	Pittcon introduced some significant changes in 2018. The most visible was the decrease in time for the exhibition from four to three days. On Tuesday (the first day), the exhibition floor was very active with what amounted to pent-up energy. However, we must also point out a decrease in the size of the exposition and the absence of some large vendors. There were large seating areas for interactions and even seminars, and the return of the Lab Gauntlet, where vendors present application solutions using their tools. The Gauntlet is a successful addition to the show, with a lot of energy and interest flowing down the aisle. Some presentations (Thermo Fisher Scientific) showed their new products in the Gauntlet, too, making it a continuation, in effect, of booth presentations.

	Although Pittcon remains an important venue for the introduction of new products over the past few years, vendors are also increasingly announcing new products outside Pittcon. We therefore accept any new products announced during the past year for inclusion in this review, which covers new instruments, components, and accessories announced by vendors during 2017–2018.

	Attendance in 2016 was 12,841 and attendance for 2017 was 14,144. This year's attendance was reported as 11,415 (1). The increase seen last year was attributed mainly to the improving economy. It's not clear whether or not the attendance number reflects only the reduced number of days for the show. Last year we hypothesized that Pittcon attendance might be what economists would call a "lagging indicator."

	The exposition featured 714 exhibiting companies occupying 1404 booths, somewhat lower than last year's figure of 787 exhibiting companies. The reduced number of exhibitors might possibly be a result of the reduction of exhibition days to three. Of these companies, 93 were reported as being first-time exhibitors. Increased attendance may persuade more companies to exhibit in the future, as well.

	There is a healthy pipeline of new products coming from a wide variety of vendors and application areas. It is good to see continued development around the classic techniques, like near-IR, mid-IR, and Raman spectroscopy. There is a lot of activity around accessories, too, where vendors strive to meet user-specific applications.

	For the last couple of years, Pittcon did not present Editor’s Choice awards as it had done for many years previously. Last year, that event was replaced with Pittcon Total Excellence Awards. This year the Excellence Awards seem to have settled down into that new format. The award selection committee consisted of a blue chip panel of experts who evaluated the entries based on “ingenuity, creativity, implementation, and outcomes.” Companies are now segregated into small, medium, and large companies based on sales figures so that they can only compete with others in their class. Therefore, there were three awards of each type: gold, silver, and bronze. We are pleased to note that the following spectroscopy companies were winners of the Excellence Awards: In the $10,000,000– $100,000,000 sales category, B&W Tek won gold for its STRaman portable Raman analyzer; Metrohm won silver for its 946 Portable VA voltammetric analyzer; and CEM Corporation won bronze for its EDGE extraction system for sample preparation. In the greater than $100,000,000 sales category, Horiba Scientific won gold for its Duetta fluorescence and absorbance spectrometer (listed in Table III) and Shimadzu Scientific Instruments took home bronze for its IRSpirit FT-IR spectrometer (listed in Table V).

	The review that follows is categorized by wavelength region or type of spectroscopy (such as mid-IR, X-ray, and so forth). We arranged our review to allow readers to compare instruments from different manufacturers, although this process sometimes groups handheld instruments with high-end research tools. The categories used to classify the products are

	Accessories
	Atomic spectroscopy
	Components
	Fluorescence
	Mass spectrometry (MS)
	Mid-infrared spectroscopy
	Near-infrared (NIR) spectroscopy
	Nuclear magnetic resonance (NMR)
	Raman spectroscopy
	Software
	UV–visible spectroscopy
	X-ray (includes higher frequencies)

	Categories fluctuate from year to year, depending upon trends in the submissions and in the industry. The core spectroscopy headings are usually consistent, but marginal categories such as “imaging” have been transient and had no entries this year. Fluorescence has been absent for several years, and we are pleased to see it back as a category. As in the past, “accessories” are tools used in conjunction with an instrument (such as a sample preparation or ATR device), while “components” (such as lasers or detectors) are used within an instrument. The “software” category includes instrument control, collection and data processing programs, as well as products for storage and transmission of data and also collections of data, such as databases (libraries).

	Instrumentation is evolving, like the telephone, to cover a wider array of scientific problems. The high-end instrumentation remains solid, with mainly evolutionary changes: witness the increasing resolution of mass spectrometers. Meanwhile, another trend is reduction in size. For example, routine and field analysis is increasingly being taken over by handheld or portable devices, a trend that seems to be continuing.

	The growth we saw in Raman last year continues, with ongoing improvements in the tools and a number of new systems being launched. New generations of small Raman spectrometers continue to appear. Both commercial and academic users of Raman are seeing more laser, detector, and optical options. With this market slated to maintain double-digit growth, we can expect this trend to continue for some time.

	Near-IR (NIR) spectroscopy remains a solid method for many analyses, and there is lots of activity in this area. Multiple vendors introduced new tools for NIR, while others have modified existing products to extend their capabilities. The NIR field is not as strong of a growth vector for commercial vendors as Raman. However, it is a core piece of many industrial processes, indicating that we will also see continued developments and improvements in this line.

	The largest number of new submissions came from the accessories area. As always, accessories divide generally into sample preparation tools and items intended for use in probe systems. The key factor, as always, for these vendors has been to recognize a need (like lowcost microtoming) and then devise a targeted tool.

	Instruments are also evolving to detect ever-smaller sample sizes. More spectrometers are now reaching the same scales, such as the coupling of Raman and infrared to atomic force microscopes. In addition to microscopes being attached to various optical spectrometers, other couplings of instruments are starting to appear, such as combined terahertz and FT-IR (mid-IR) spectrometers, and combined mid-IR and Raman in a single unit. The ultimate in small sample size is, of course, the ability to detect and measure the spectrum of a single molecule. We also note that, despite reports from academia about single-molecule detection and characterization, no commercial device has yet appeared in that arena.

	Three broad themes emerged from the new products announced to 

and during Pittcon. Classic techniques saw activity. For instance, announcements included multiple tools for the age-old problem of sample preparation (grinding and pressing of samples) and new offerings in inductively coupled plasma (ICP) and FT-IR microscopy. There should be little surprise here-many of the problems faced by today’s laboratory workers are the same as those from 20–30 years ago. In spite of exciting developments at the cutting edge, there is plenty of basic chemistry that still needs to be done.

	Second, while many vendors are marketing instruments similar to those from years past, the surge in new software developments is continuing. Developments center on two problems: matching the user interface to the problem and lowering sampling barriers. Enlarged databases and new algorithms are combining to provide customized, useful reports. Terrain-following software in microscopy is relieving the problem of focusing on an irregular sample over a large area. And collaboration is being enhanced using video cameras and touch screens to replace single-user eyepieces, allowing local and remote users to tackle problems as a team.

	Third, Raman spectroscopy offerings continue to expand. At Pittcon, it seemed every aisle had Raman vendors differentiating their products by size (handheld, portable, or benchtop) and performance. The Raman effect was first observed in 1928, so Raman has had a long development cycle because of some very specific requirements that had to be met to make it a commercially viable technique. The most crucial tool has been the laser, and now many vendors provide multiple diode laser solutions in small packages with low power needs. Vendors can take the ingredients-lasers, miniaturized diffraction elements, and multichannel detectors-and combine them in a particular form factor to address a specific market.

	We noted a trend a few years back toward application-specific analyzers. Although this trend seems to have slowed, many vendors have noted how their tools combine in certain markets. See, for example, the new Bruker electron spin resonance beer analyzer, and the Brimrose Seedmeister NIR analyzer. A new field around cannabinoids is growing. Legalization is opening up new applications in this burgeoning new commodity, which has increased the market for quality control and regulatory compliance. This rapidly evolving field historically is populated by highend instruments-for example, gas chromatography–mass spectrometry (GC–MS)-but now seeking low-cost solutions.

	In each section of the review, every category lists products with a brief synopsis of capabilities as well as a more extensive list of capabilities.

	It is always inevitable that some categories include products that might arguably be classified elsewhere, especially in regard to accessories, components, and software. Some hyphenated techniques, such as inductively coupled plasma–mass spectrometry (ICP-MS) could legitimately be listed in either location. In such cases, the authors usually respected the classification given by the manufacturer.

	We also endeavored to provide a synopsis of salient features for each product, or at least as much as could be included in limited space. We follow a “features–benefit” format, so that not only are the key features of a given instrument described, but also the meaningfulness of those features to the user. Also, readers can search by company name or product category in Table I, which references the headings where the content will be found.

	This year in the atomic spectroscopy category (Table II), several new ICP instruments with optical emission spectrometry (OES) or MS detection were introduced (PerkinElmer, LECO, and Thermo Fisher Scientific). Like other established methods, the main goals appear to be better detection limits and usability. Spectro Analytical also showed new portable units for the analysis of metals in the field. In recent years, we saw laser-induced breakdown spectroscopy (LIBS) moving in this direction as well.

	LECO has full wavelength coverage from 160 to 460 nm, with 50 pm resolution, to differentiate complex features of bulk spectra.

	McPherson provides flat field and aberration corrected optics with better extreme UV and soft X-ray spectra. Narrow symmetrical spectral lines help resolve and discriminate spectral signatures at very short wavelengths. The systems include high vacuum housing, optimized coatings, and sensitive cooled charge coupled device (CCD) detectors.

	PerkinElmer has the smallest ICP system on the market, with patented Flat Plate plasma technology that uses half the argon of other systems.

	Spectro Analytical Instruments has a new advanced, portable OES analyzer that delivers many of the advantages of the company’s flagship mobile Spectrotest OES analyzer in a smaller, lighter unit.

	Probably the most innovative and exciting development in years for fluorescence (Table III) emerged from Horiba Scientific-an instrument that won best in show at Pittcon. A two-dimensional design allows the Duetta fluorescence and absorbance spectrometer to simultaneously collect-at amazing speeds- UV–vis–NIR absorbance spectra at the same time as the fluorescence is captured. This device should prove to be valuable in drug discovery laboratories and related fields in biophysics. A second new instrument, from PicoQuant, provides access to steady-state, lifetime, and phosphorescence.

	Horiba’s instrument can measure fluorescence and UV–vis absorbance spectra, and can also do both simultaneously

	PicoQuant shows its FluoTime 300 fully automated, high-performance fluorescence spectrometer for steadystate, lifetime, and phosphorescence measurements.

	A few new products were introduced in the MS category (Table IV) this year. For example, Shimadzu, introduced a matrix-assisted laser desorption–ionization time-of-flight (MALDI-TOF

front-end designed for efficient sample introduction.

	Bruker Daltonik offers a TOF mass spectrometer specialized to improve the analysis of the proteome.

	Excellims shows a compact ion mobility analyzer for analytical laboratories and at-line applications. Combining high resolution (

> 70) and soft electrospray ionization to allow for the introduction of a wide range of compounds, the GA2200 analyzer permits chemical analysis of mixtures in seconds.

	Shimadzu provides a benchtop TOF mass spectrometer that improves laboratory efficiency and accelerates analysis through a newly designed load–lock system for rapid sample target introduction and a solid-state laser for fast data acquisition speeds.

	In mid-IR (Table V), three different approaches to the infrared analysis of materials are reported in this year’s new developments. Quantum cascade lasers continue to appear in new configurations. The crowded field of small benchtop instruments saw new and refreshed instruments from Shimadzu Scientific Instruments and Bruker Daltonik, respectively. And a solid-state instrument designed for hazardous environments was introduced by Quantum Analytics.

	Block Engineering has configured QC lasers for a breakthrough in openpath chemical detection and measurement that simultaneously offers detection of large numbers of chemicals (hundreds or even thousands), resulting from the use of world-record, ultrawidely tunable quantum cascade lasers, and a new class of sophisticated detection algorithms.

	Bruker offers a multispectral range FT-IR R&D spectrometer with many innovative features, including detector technology that allows for up to seven internal software-controlled detectors. A unique additional channel allows for mid-IR transmittance measurements without removing research setups from the main sample compartment.

	Quantum Analytics has introduced a solid-state instrument certified for use in hazardous and explosive environments. It is mounted directly on, or in-line with, manufacturing vessels, and excels at continuous monitoring of industrial liquids and slurries. Impervious to vibration, this in situ sensor monitors reactions live.

	Shimadzu Scientific Instruments provides unmatched functionality in its class of compact instruments with a design that allows access and a standard-sized sample compartment that accommodates a wide range of existing accessories.

	This year, there was a lot of activity around NIR instrumentation (Table VI). Portability was a major theme of offerings from companies such as BaySpec, Spectral Evolution, and Spectral Engines. Food-targeted analyzers were also developed by Brimrose and Avantes, showing that the analyzer theme seen some years back continues in the NIR space, but at a slowed pace. Adaptation of existing equipment into the NIR space was also shown by PerkinElmer.

	Another general trend that started off slowly a while back and seems to be continuing is for manufacturers to provide instruments precalibrated for the commodities (and the analytes in those commodities) that their customers want to measure.

	Avantes has new and improved versions of NIR spectrometers that are based on a 100-mm optical bench with a numerical aperture (NA) of 0.13 that offer an optimal balance between resolution and sensitivity. The 2.5-HSC series spectrometers feature 256- or 512-pixel InGaAs detectors and are available in multiple configurations.

	Bayspec has the world’s smartest palm spectrometer, the Breeze spectrometer for the 400–1700 nm range. Featuring proprietary miniaturized optics, the spectrometer is highly efficient for maximum sensitivity with ultrafast acquisition.

	The Brimrose Seedmeister Mark III acousto-optic tunable filter (AOTF)-NIR spectrometer is focused specifically on the comprehensive understanding of peanuts. The unit is able through nondestructive testing to fully characterize such properties as protein, moisture, starch, oleic, and linoleic oils.

	The Galaxy QuasIR 1000 NIR spectrometer ensures direct calibration transfer without the frustration of standardizing instruments or adjusting models to accommodate excessive instrument variability. Edible oils, lubricants, and fuels can be easily analyzed for quality control or adulteration.

	PerkinElmer’s Spectrum Two N spectrometer is a high-performance, robust, and transportable FT-NIR system platform enabling simple, reliable NIR analyses, ideal for laboratories that need to combine high-end performance with the ease-ofuse features of a portable instrument.

	Si-Ware Systems provides a compact, low-cost FT-IR spectral sensor that delivers the spectral response of the light absorbed by materials for quantification, qualification, or identification.

	Spectral Engines provides an NIR sensor that incorporates a Fabry-Perot microelectromechanical systems (MEMS) sensor and light sources. The NIRone NIR sensor has a large dynamic range and stability in the face of temperature changes and vibration, and also offers a battery-powered scanner that pairs wireless and Bluetooth connectivity with the NIRone NIR sensor and light sources.

	Spectral Evolution has its smallest, lightest, full-featured field spectroradiometer that has a spectral range of 320–1100 nm and can be used with a laptop or handheld microcomputer, or as a standalone instrument with its built-in keypad and liquid crystal display (LCD). It provides a 25°, 1-m fiber-optic cable with industry-standard FC connections and allows users to select from 1, 2, 3, 4, 5, 8, and 10° field of view lenses or connect to a handheld contact probe or unique leaf clip.

	Only one manufacturer, Magritek, showed new instrumentation, continuing to develop the benchtop NMR area. This area (Table VII) continues to show increasing promise as the fields increase, improving sensitivity and providing access to more nuclei. There are also related developments in NMR–electron spin resonance (ESR) methods applied to specific markets.

	Bruker’s Beer Freshness solution, consisting of an ESR instrument with custom software and database, is the result of a collaboration between Bruker and FlavorActiv. The solution aims to optimize brewing operations and storage conditions to provide maximum antioxidant content in packaged beer.

	Magritek has a carbon benchtop NMR spectrometer that provides remarkable 60-MHz NMR performance in a compact, benchtop instrument including 1D and 2D NMR experiment capability, with 

	Recent trade shows like Pittcon have seen many new Raman systems being shown (Table VIII). While fewer new devices appeared this year, there were innovations, especially around small scale and original equipment manufacturer (OEM) instruments. The most unusual entrant this year, from TimeGate Instruments, strives to eliminate the old enemy of Raman- fluorescence-through time gating of the signal.

	Anton Paar has a compact, benchtop Raman platform that integrates a volume phase grating for high light throughput.

	Horiba Scientific manufactures and combines a spectrometer, laser, and acquisition computer in one instrument that fiber-optically couples to a Raman ball probe to obtain high-quality Raman measurements without multiple boxes or need to focus.

	Metrohm shows the smallest handheld Raman analyzer available, designed to bring the precision of laboratory analysis to first responders in the field.

	Raman process instruments from Spectra Solutions include a high- throughput spectrograph with multifiber input and thermoelectrically cooled CCD (-60 °C) and can monitor up to six different probes simultaneously. Each probe is connected to its own laser source and rack-mountable instrument housing.

	The tec5USA MultiSpec Raman system is a versatile platform for laboratory and process measurements. It features a 785-nm laser (class 3B) variable from 50 to 500 mW, and a thermoelectrically cooled high-resolution CCD detector.

	Timegate Instruments eliminates background sample fluorescence using a combination of a picosecond laser and picosecond detector. The Raman scattering from the pulsed laser is prompt, and the fluorescence, which is delayed, is gated out by the ultrafast detector.

	Wasatch Photonics offers a drop-in OEM module that delivers high-performance Raman spectroscopy in a robust, compact package.

	WITec’s Active Stabilization software feature optimizes the Raman signal by ensuring that the focus between the microscope objective and sample is maintained, even in the face of changes in the environment.

	UV–vis instruments (Table IX) are workhorses in the analytical laboratory. With a long history of applications and new ones arising-especially in the pharmaceutical world-many vendors continue to develop these tools. The improvements center around speed of the analysis, decreasing the sample size, and increasing the sensitivity in a smaller instrument.

	Avantes presents two new instruments, the Hero and the MKII UV–vis spectrometers. The former instrument emphasizes spectral sensitivity, and the latter features a detector array with more pixels for better spatial resolution.

	Cecil Instruments has a double-beam instrument that can perform preprogrammed assays.

	Ibsen’s Freedom C spectrometer introduces a new 4096px detector that enables higher resolution for the UV region down to 0.15 nm.

	Wasatch Photonics has a new UV–vis spectrometer series that delivers analytical laboratory-grade performance in a compact footprint. Its proprietary transmission volume phase holographic grating design maximizes efficiency and reduces stray light to extremely low levels.

	Both companies in this section of the review introduce X-ray equipment (Table X) that stresses small spot sizes and speed of response.

	Malvern Panalytical (formerly Malvern) supplies the Epsilon 1 analyzer for small-spot X-ray analysis, which offers users the capability to analyze samples with a 1-mm measurement spot.

	The Midex MID05 energy dispersive X-ray fluorescence spectrometer from Spectro Analytical Instruments is designed to provide exceptional performance, high precision, and accuracy for a wide range of precious metal alloys, with testing times as low as 15 s, for more than 30 elements backed by extensive factory calibrations.

	Software (Table XI) consists of several different, albeit related, types of products. The first, and arguably the main type, is actual computer programs (that is, the sequences of instructions computers use to carry out their functions).

	A large number of new software products appeared this year. The software interface and the attainment of results are now the core of user experience. Clearly, helping users move rapidly from a sample to a result is becoming a major goal of both instrument developers and pure software companies. There is also movement in the area of spectral libraries (vibrational and MS), as new materials and new demands are causing the industry to reach for new reference standards to hit customer targets.

	The second type of product consists of collections of various types of data. One important subcategory of this product type consists of actual databases- sets of related data that can be used in a manner similar to dictionaries or encyclopedias (as compendia of important facts and relationships among those facts).

Articles

Feature

Our annual review of spectroscopy products, broken down into the following categories: Atomic Spectroscopy, Florescence, Mass Spectrometry, Mid-IR, NIR, NMR and ESR, Raman, UV-vis, X-ray, Software, Accessories, Components

Review of New Spectroscopic Instrumentation for 2018

As a follow up to March 2018's "Atomic Perspectives" column, which provided guidance on how to choose the optimum technique for carrying out the measurement of elemental impurities in pharmaceuticals, this month's installment takes a look at the implementation of the new 

International Conference for Harmonization (ICH)

 guidelines for this method from an historical perspective. This column provides insight into these changes and takes a look at the challenges and opportunities that lay ahead as the industry embraces this new methodology.

	The identification and quantification of elemental impurities in pharmaceuticals have been a challenge for many years. In the late 1800s and early 20th century, lead was an issue because it was used in the production of solder, and, absent the good manufacturing practices controls that are in place today, metals from manufacturing and processing equipment posed potential problems, as did mined excipients that could carry with them elements such as arsenic, lead, cadmium, and mercury.

	The United States Pharmacopeia (USP) first addressed this issue in 1908, with the publication of what became general chapter <231> - Heavy Metals. This test typically involves the high-temperature digestion of the material of interest followed by sulfide precipitation of the metals of interest. The specification is based on comparison of the color of the resulting precipitate to the color of a lead sulfide precipitate prepared at the level of interest (typically 10 or 20 ppm). There are, of course, many issues with this test. The test generates hydrogen sulfide, which can be highly toxic, and in the USP method, does this through the use of thioacetamide, which has its own safety issues. The test was initially designed to detect lead, mercury, bismuth, arsenic, antimony, tin, cadmium, silver, copper, and molybdenum. Not included are common components of manufacturing equipment such as nickel and vanadium, or common catalysts such as platinum or palladium. In addition, the test is a screening test and is not element specific, and since each precipitate has a different color (and most are lighter than the color of lead sulfide), even its use as a total metal limits test can be questioned. A final issue is that the test is based on visual acuity, rather than being toxicologically based. For a test for elements considered toxic, it is far preferred that it be based not on what one observes, but rather on what levels are of toxicological concern.

	Given all these issues, why did the test remain as an official test in the USP until January 2018, approximately 110 years after its introduction? The primary reason is likely that there was not an industry-wide, globally accepted test to replace it. For all its faults, the methodology of general chapter <231> was well understood, routinely used by the industry, and was harmonized with the European and Japanese pharmacopeias. The winds of change began with the publication in 1995 of a Stimuli to the Revision Process article in the 

 by Katherine Blake (1). In this article, she noted that often 50% of the metal of interest was lost in the ash process, and that there was essentially zero recovery for mercury, one of the more toxic and common elements of interest. In 2000, Dr. Taibang Wang made similar observations in an article in the 

Journal of Pharmaceutical and Biomedical Analysis

, where he noted "Although still widely accepted and used in the pharmaceutical industry, these methods based on the intensity of color of sulfide precipitation are non-specific, labor intensive, and more often than hoped, yield low recoveries or no recoveries at all" (2). Then, in 2004, Nancy Lewen and coworkers directly compared the recoveries of 14 elements using 

 <231> Method II and inductively coupled plasma-mass spectrometry (ICP-MS). Consistent with the other two articles, this study showed a number of recoveries around 50%, with recoveries of less than 10% for Se, Sn, Sb, and Ru with, as anticipated, no recovery at all for Hg, as exemplified in Figure 1 (3).


	Figure 1: Comparisons between ICP-MS and Method II described in USP Chapter <231> (3).

	This work set the stage for the establishment at USP of a series of committees and expert panels, beginning in earnest with the 2005–2010 revision cycle to update the concept of heavy metals testing. The process built on an Institute of Medicine meeting commissioned by USP in 2008, and on a document issued by the European Medicines Agency (EMA), which developed guidelines on the control of residual catalysts in pharmaceuticals with the goal of establishing limits based on toxicological safety assessments of common catalytic elements. This work began as early as 1998 and resulted in a guideline that was officially implemented in 2008 (4).

	Building on all this, USP published in the 

 a proposed general chapter on Inorganic Impurities: Heavy Metals that was the early precursor to general chapter <232> - Elemental Impurities – Limits, and <233> - Elemental Impurities – Procedures (5). This USP initiative led to the desire by the pharmaceutical industry participants to have, as with general chapter <231>, a chapter that was harmonized across the pharmacopeias in the International Conference for Harmonization (ICH) region (at a minimum, the United States, Europe, and Japan). The result of this harmonization initiative was the ICH Q3D expert working group, and the final output was the 

 guideline on elemental impurities, with the step 4 document posted to the ICH website in December 2014 (6). The guideline was implemented for new drug products by the U.S. Food and Drug Administration (FDA) beginning in July, 2016, and for all drug products, new and existing, in the 

 in January 2018, concurrent with omission from the 

 of general chapter <231>. General chapter <232> applies only to drug products and not to drug substances or excipients, since without knowledge of issues such as dose and route of administration, establishment of specifications for these materials is not possible.

	ICH Q3D focused on the establishment of a list of elements of toxicological concern and their limits in oral, parenteral, and inhalational dosage forms as well as a risk-based approach for demonstrating absence of the various metals and compliance with the specification. An extensive body of training materials is available to help practitioners understand the scope of the guideline, the concept of a risk-based approach, and how to think about issues such as the calculations of concentrations in the drug product and extension to other dosage forms (7). Because the entire process is risk based, testing is only one of many ways by which compliance with the standard can be demonstrated. The full list of permitted daily exposure (PDE) elemental limits defined in 

 Step 4 guideline are shown in Table I. Note that the classification is based on their toxicological impact (a combination of toxicity and likelihood of occurrence), with Class 1 and 2A elements considered the most significant.

	Testing of drug products and excipients was not discussed in detail by the ICH Q3D working group. Rather, it was left to the individual pharmacopeias to work out their own procedures, with the goal of long-term harmonization of the final results. In the 

, general chapter <233> describes two procedures, inductively coupled plasma–optical emission spectroscopy (ICP-OES) and ICP-MS, along with system suitability and validation requirements for these tests and any alternative tests. It is noted that any test that meets the validation requirements and is otherwise fit for purpose can be used instead of the two proposed tests.

 general chapters, and the elimination of 

 <231> are major steps forward in the analysis of elemental impurities in pharmaceuticals. There is now broad agreement across the pharmaceutical industry and across many countries about the elements of toxicological concern and the levels at which they should be controlled.

	Let's get back to the earlier question: Why did it take 110 years to get here? The simple answer is that it took that amount of time and innovation for the right technology to be developed and for the technology to be widely available and accepted by the pharmaceutical industry. For a drug product specification to be accepted as a public standard (as opposed to a private standard between a pharmaceutical company and a regulatory body where the company can perhaps propose a sophisticated test not readily available), any proposed test needs to be well established, well accepted by the industry, reliable, and broadly available, either in house or though contract research organizations.

	Until the last several years, these requirements simply hadn't been met. Only a few technologies are capable of meeting the requirements of general chapters <232> and <233>. While ICP-OES was widely available, there are situations, especially for low-dose drugs or parenteral or inhalational drugs, where a number of elements need to be measured or controlled; ICP-MS is the option of choice. Only recently have the software, hardware, price, and availability-either in house or through contract research organizations-been there to make broad applicability across the industry feasible.

	In addition, a suite of new technologies, sampling accessories, and data processing tools is making life easier for pharmaceutical companies that are working in a good manufacturing practice (GMP) environment. Some of these are aimed at laboratories that are looking to maximize sample throughput by using productivity enhancement tools to automate the full suite of quality control and spike recovery testing procedures described in Chapter <233>, as well as to ensure that the calculations are done correctly and properly documented, in order to minimize operator interaction, and allow the analyst to focus on other tasks.

	Other areas that have been addressed include software tools to provide data in a suitable compliant form for regulatory submission and inspection. For example, any analytical instrument used for measuring pharmaceuticals must also comply with the FDA's 21 

 Part 11 regulations to ensure the integrity of any electronic records that are generated. The instrument's software control and data handling must therefore incorporate tools to maintain the integrity of the analytical method and subsequent results and provide transparency to data generation, including support for audit trails as well as security features to ensure that alterations cannot be made without a clear explanation of the process. It's therefore very important that the instrument and its software provide the necessary support to meet these kinds of demands in the highly regulated pharmaceutical industry environment.

	The widespread availability of this technology, and the study and publication of results of the levels of elemental impurities in drug substances and excipients will likely lead to less testing of materials in the long run. Currently, many drug substances and excipients are being tested for the first time. As databases are developed and made public, many excipients and drug substances may be demonstrated to be of sufficiently low concern that they will no longer need to be considered in a risk assessment, and risk assessments may be limited to perhaps a few specific mined excipients, or materials used in very high quantities in a dose form. Thus testing, which is already only one part of an overall risk assessment, may become even less frequent in the future. This development is an example of the technology providing a breakthrough in the assessment of safety, and soon being relegated to a role as a tool for specific purposes and very seldom, if ever, as a tool for routine monitoring of drug products.

	What's left to get to the point where the industry feels that the risks of elemental impurities are well understood and controlled and only minimal levels of testing are necessary? A key piece will be accurate measurement of the levels of elemental impurities in drug substances and excipients, and the broad availability of this information. Another key to making this happen is the generation of good data by the people producing data on the various drug substances, excipients, and drug products. The industry needs good data upon which to make decisions, and the generation of such data for elemental impurities is quite difficult. Issues such as sample homogeneity, sample contamination, instrument sensitivity, and instrument artifacts all play a role in the generation of reliable data.

	Sample contamination is of particular concern. As discussed above, the elements of most concern (for example, As, Pb, Cd, Hg, Ni, V, and Co) have been selected because they are both potentially toxic and widely found in the laboratory or in nature, whether in glassware, equipment, reagents, or even clothing or accessories worn by analysts or others in the laboratory. Accessories containing metals can be of particular concern. In addition, reagents such as concentrated acids need to be tested to be free of metals to avoid sample contamination. At the trace levels at which these elements are being detected, very low levels of contamination can lead to false positive results, which in turn can result in additional testing and rework.

	Similarly, ICP-MS instrumental artifacts can also lead to erroneous results, such as the effect of the 

Cl polyatomic spectral interference on the measurement of 

As. This effect is of particular concern if chloride is present in the sample matrix or if concentrated hydrochloric acid is used for the digestion of the sample. The chloride ions will combine with the argon from the plasma to form an argon chloride spectral interference that will significantly interfere with the monoisotopic arsenic ion at mass 75. This effect can be minimized by avoiding hydrochloric acid in the digestion procedure, but if this is not possible, or chloride is present in the drug product, an ICP-MS system fitted with a collision–reaction cell is a very important tool to have at your disposal to help prevent the formation of the interference.

	We have come a long way in the assessment of risk of toxicity from low-level trace elements in pharmaceuticals from the days of sulfide precipitation and comparison to a lead sulfide standard. The new risk assessment strategies and tools-such as closed-vessel digestion to provide analyzable samples with minimal analyte loss and ICP-MS to provide the requisite sensitivity and selectivity-have enabled the industry to quantify the elemental impurity levels in drug substances, excipients, and drug products and reach a point where solid, risk-based assessments can be made with only minimal testing needed in the long term.

	This month's column has been adapted from Robert Thomas's new book (8).

	(4) European Medicines Agency, Committee for Medicinal Products for Human Use. 2008. Guideline on the specification limits for residues of metal catalysts or metal reagents. Doc. Ref. EMEA/CHMP/SWP/4446/20007.

	(5) General Chapter on Inorganic Impurities: Heavy Metals, PF 34(5), 2008.

http://www.ich.org/products/guidelines/quality/article/quality-guidelines.html

Measuring Elemental Impurities in Pharmaceuticals: A Practical Guide

 (CRC Press, Boca Raton, Florida, 2018). ISBN13:978-1-138-19796.

 is a consultant in analytical, compendial, bioanalytical, and quality-related issues. He has worked in the pharmaceutical industry for more than 40 years. As a former Vice President at US Pharmacopeia, he led the initiatives to maintain, update, and redesign the General Chapters, and also served as a member of the ICH Q3D Expert Working Group on metal impurities. He has advanced degrees in Physical Chemistry from Cornell University and is a member of the American Chemical Society (ACS) and past president of the American Association of Pharmaceutical Scientists (AAPS).

 is principal of Scientific Solutions, a consulting company that serves the application and writing needs of the trace element user community. He has worked in the field of atomic and mass spectroscopy for more than 40 years and has written over 80 technical publications including a 15-part tutorial series on ICP-MS. He recently completed his fourth textbook entitled 

. He has an advanced degree in analytical chemistry from the University of Wales, UK, and is also a Fellow of the Royal Society of Chemistry (FRSC) and a Chartered Chemist (CChem). He has served on the ACS Committee on Analytical Reagents for the past 17 years.

Atomic Perspectives

A look at the implementation of the new United States Pharmacopeia (USP) chapters and the International Conference for Harmonization (ICH) guidelines for elemental impurities from an historical perspective, providing insight into the changes and considering the challenges and opportunities that lie ahead as the industry embraces the new methodology.

From Heavy Metals Testing to the Measurement of Elemental Impurities in Pharmaceuticals: Over 100 Years in Making the Change

Carboxylates are made by reacting carboxylic acids with strong bases such as inorganic hydroxides. The resultant salts are commonly used as cleansers, including in common bar soap-hence the pun in the title. Carboxylates contain two unique carbon–oxygen "bond and half" linkages that coordinate with a metal ion to give two strong infrared peaks, which make them easy to see.

	So far in our investigation of the infrared spectroscopy of the carbonyl functional group, we have looked at ketones, aldehydes, carboxylic acids, and acid anhydrides (1–4). Acid anhydrides are derivatives of carboxylic acids and are made by reacting two acid molecules and splitting off an atom of water (4). Carboxylates are another derivative of carboxylic acids, and they are made via a classic acid–base reaction of a carboxylic acid with a strong base such as a hydroxide. Such a reaction is shown in Figure 1.

	As in the synthesis of acid anhydrides, one of the driving forces for the reaction is the splitting-off of a molecule of water. Note in Figure 1 that the carboxylate functional group contains ionic bonding; there is a formal positive charge on the metal ion and a negative charge on the carboxylate. Also shown in Figure 1 is that the metal ion from the hydroxide coordinates with the two oxygens from the carboxylic acid to form an unusual bonding arrangement with two equivalent carbon–oxygen bonds. We will call this the "-CO

" group because it contains two carbon–oxygen bonds of the same bond order, similar to carbon dioxide (O=C=O).


	Figure 1: The reaction of a carboxylic acid with sodium hydroxide to give a carboxylate and water.

	Carboxylates are named after the acid and base used to make them. Thus, the reaction of acetic acid and sodium hydroxide would yield sodium acetate. A classic acid–base reaction, such as between NaOH and HCl, forms a salt and water. Carboxylates are sometimes referred to as 

 because a carboxylate is a salt formed by the reaction of a carboxylic acid with a base.

	Carboxylates are unusual in that they frequently have a polar end consisting of the carboxylate, and a nonpolar end such as an alkyl chain. This structure makes them uniquely capable of solubilizing oil and dirt into water, which is why they are commonly used as cleaning agents (explaining the bad pun in the title of this column). In fact, sodium stearate, the product of the reaction of sodium hydroxide and stearic acid, is also known as hand soap.

	The infrared spectrum of a carboxylate, zinc stearate, is shown in Figure 2. This molecule is made by reacting two equivalents of stearic acid with the dibasic zinc hydroxide, yielding a molecule with two carboxylate moieties.


	Figure 2: The infrared spectrum of zinc stearate (C

	Because carboxylates contain neither a C=O bond nor a C-O bond, they will not contain a carbonyl stretching peak around 1700 cm

 (1) (going forward assume all peak positions are in wavenumber units), or a C-O stretch between 1300 and 1000 (5). There are two intense peaks at 1538 and 1398 in Figure 2 that stick down out of the spectrum like canine teeth. These are from the asymmetric and symmetric stretches of the -CO

 group. Generally, these two peaks fall from 1650 to 1540 and 1450 to 1360, respectively. Unlike the C=O group, carboxylate stretches are insensitive as to whether saturated or unsaturated carbons are attached to them.

	The carbon–oxygen bond order in the -CO

 group is about one and half, and the infrared spectrum shown in Figure 2 will help prove this. A C=O stretch falls at about 1700 (1), and a C-O stretch typically falls at about 1200 (5). Theoretically then a C-O "bond and a half stretch" might fall at the average peak position of these two carbon–oxygen stretching vibrations. The average of 1700 and 1200 is 1450, close to where the carboxylate stretching peaks fall. This close agreement indicates that the carbon–oxygen bond order in carboxylates is approximately 1.5.

	Because carboxylates contain positive and negative charges, they are highly polar and have a large dipole moment. Recall from the first installment of this column that one of the characteristics that determine infrared peak positions is the change in dipole moment with respect to bond distance during a vibration, or dµ/d

 group stretch asymmetrically and symmetrically there is a large value of dµ/d

. This attribute is why the pair of carboxylate stretching peaks are so intense.

	In theory, one could identify the metal ion in a carboxylate from its mid-infrared spectrum. Recall, however, that as the mass of the atoms in a functional group goes up peak position goes down (7). Most metal atoms are heavier than the hydrogen, carbon, and oxygen atoms typically found in organic molecules. Thus, the metal–oxygen stretching and bending peaks that might help us determine the metal ion in a carboxylate fall below 400, out of range of most mid-infrared Fourier transform-infrared (FT-IR) spectrometers. Now, carboxylates with different metal atoms will have different infrared spectra because they have different chemical structures (7), but the inability of most FT-IRs to see metal–oxygen peaks makes it difficult to determine the metal ion from the infrared spectrum by itself. In this case, consultation of reference spectra, a library search, or a metals analysis of the sample using some form of atomic spectroscopy will be needed.

	In the chemical structure of zinc stearate shown in Figure 2 you can see that there are two very long alkyl chains, together whose CH

 ratio is 16. Recall that the relative intensity of the methylene asymmetric stretch compared to the methyl symmetric stretch is proportional to the CH

 ratio for a molecule (7). As can be seen in Figure 2, the CH

 asymmetric stretching peak at 2916 is significantly larger than the CH

 asymmetric stretching peak at 2959, as expected.

	Also note in Figure 2 that from 1400 down to 400 there are a number of weak to medium intensity peaks. These peaks include C-C stretching bands (8). Under normal circumstances these vibrations would have small values of dµ/d

 giving difficult to see peaks. Because of the highly polar nature of the carboxylate group, however, the alkyl chain itself is somewhat polarized, which increases dµ/d

 for its vibrations and yields the plethora of peaks seen. The diagnostic group wavenumbers for carboxylates are listed in Table I.

	Carboxylates are made by reacting a carboxylic acid with a strong base such as a hydroxide. The structure of the resultant functional group contains a negatively charged -CO

 group and a positively charged metal atom, and hence is highly polar. As a result, carboxylates have a large dipole moment and give two intense peaks, assigned as the asymmetric and symmetric -CO

 stretches at 1650–1540 and 1450–1360, respectively. The positions of these two peaks indicate that the bond order of -CO

Infrared Spectral Interpretation: A Systematic Approach

	All of our "IR Spectral Interpretation" quizzes are available online. If you are interested in testing your skills and taking additional "IR Spectral Intepretation" quizzes, please visit 

www.spectroscopyonline.com/ir-spectral-interpretation-workshop-0

 has more than three decades of experience as an infrared spectroscopist. He has published numerous peer reviewed papers and has written three books on the subject: 

Quantitative Spectroscopy: Theory and Practic

e published by Elsevier. As a spectroscopic trainer, he has helped thousands of people around the world improve their infrared analyses. He earned his PhD in physical chemistry from Dartmouth College. He can be reached at: 

IR Spectral Interpretation Workshop

Carboxylates are made by reacting carboxylic acids with strong bases such as inorganic hydroxides. Carboxylates contain two unique carbon–oxygen “bond and half” linkages that coordinate with a metal ion to give two strong infrared peaks, which make them easy to see.

The Carbonyl Group, Part V: Carboxylates—Coming Clean

Advanced vibrational spectroscopic techniques such as Fourier transform infrared (FT-IR) and attenuated total reflection (ATR)-FT-IR spectroscopic imaging are important tools for understanding molecular interactions and using them to help engineer new products and processes. Sergei G. Kazarian of Imperial College London, UK, has used these advanced imaging techniques for applications as varied as studying crude oil fouling, analyzing pharmaceutical formulations in microfluidic channels, examining biological systems and biopsy samples, and investigating the pigment–oil interaction in priceless paintings at the microscale level.

One of your recent publications discusses in situ attenuated total reflection–Fourier transform infrared (ATR-FT-IR) spectroscopic imaging monitoring of asphaltene precipitation from benzene solution and crude oil induced with high-pressure CO

 (1). What makes ATR-FT-IR imaging a good choice for monitoring this process? What important conclusions were drawn from this research?

	Firstly, this research is relevant to understanding crude oil fouling, a problem that has immense economic and energy implications. In this work, we demonstrate an approach of the ATR-FT-IR spectroscopic imaging applied in situ to investigate the stability and behavior of asphaltenes dissolved in different media (benzene and crude oil) at high-pressure CO

 conditions. The precipitation of asphaltenes from benzene solutions and crude oil induced by high-pressure CO

 has been studied in situ. This is the first time that the dynamics of precipitation have been observed with ATR-FT-IR spectroscopic imaging, which was used to detect the initial stages of precipitation, to monitor the dynamics of the formation and growth of deposited particles, and to chemically analyze the constituents of the deposits observed under high-pressure conditions.

	ATR-FT-IR imaging is the method of choice to study precipitation of asphaltenes because the strong absorption of crude oil in the infrared region makes transmission FT-IR measurements very challenging. ATR-FT-IR spectroscopic imaging probes a thin layer (a few micrometers) of the sample at the bottom of the high-pressure spectroscopic cell, which provides the unique opportunity to mimic and study the behavior of crude oil at the bottom of the oil container in situ.

	It was found that asphaltenes with oxygen-containing functional groups, which are capable of forming specific Lewis acid-base interactions with CO

, have been observed to precipitate from benzene solution and crude oil at such conditions. Subsequently, based on the obtained spectroscopic data, the mechanism of CO

-induced precipitation of asphaltenes has been proposed. The obtained results may impact areas as diverse as crude oil production, oil recovery, CO

 flooding, crude oil fouling, and relevant design or operations by helping oil companies improve their energy efficiency and environmental impact (which ultimately may cut petrol prices). This research is the result of collaboration with Professor O.N. Martyanov at the Boreskov Institute of Catalysis in Novosibirsk, Russia, which celebrates its 60th anniversary this year. Notably, the Society of Applied Spectroscopy, of which I am a Fellow and Editor of its flagship journal, 

In a second study (2), you used in situ ATR–FT-IR spectroscopy for imaging pharmaceutical formulations in microfluidic channels to study drug release. What other spectroscopic techniques have been used for this type of study, and what are the advantages of your FT-IR approach over those previous techniques?

	Microformulations are of significant interest because they can be used to facilitate the development of a wide range of drug delivery systems, including tablet compacts and capsules. The following key question must be answered: How can informative data about multiple microformulations be obtained simultaneously for direct comparison in different microfluidic channels? Recently, a droplet-based microfluidic immunosensor for detection of melamine has been reported that uses a fluorescence polarization method. Ultraviolet (UV) analysis is one method that has shown potential to collect information of drug release in parallel channels using only a few milligrams of the sample. However, no spatial information about the physical or chemical processes occurring within the formulations is revealed and this approach, to date, has not been successfully applied for high-throughput screening approaches. Weitz and coworkers (3) applied fluorescence microscopy to study drug release from microparticles in a microfluidic chip using added dyes, but this approach lacks chemical specificity. However, ATR-FT-IR spectroscopic imaging, an inherently label-free approach, has shown potential for high-throughput screening of static formulations, where spatially resolved information from the different chemical components in the microformulations can be distinguished and structural changes detected, unlike in other approaches. In our macro ATR-FT-IR spectroscopic imaging approach, a combination of three exciting modern technologies was used for the first time: unique custom designed microfluidic chips; 3D printing technologies (using a microdrop system) for preparing pharmaceutical microformulations; and ATR-FT-IR chemical imaging to understand drug release and dissolution of microformulations. This approach reveals molecular-level insight into the mechanism of dissolution of microformulations and opens a new area of research with direct implications for drug delivery.

A third study in your lab involved mid-infrared spectroscopic imaging of biological systems and biopsy samples. Optical improvements were demonstrated using FT-IR microscopy when conventional sources of infrared radiation were used, as well as application of quantum cascade lasers (QCLs) (4). What challenges were overcome in this study? What are the potential benefits of this approach for clinical analysts?

	Indeed, this cited article was largely focused on discussion of optical approaches introduced in my laboratory for improving the quality of measured FT-IR spectra and the obtained spectroscopic images, as well as discussing the issues of spatial resolution (5). The former discussion includes a demonstration of our pioneering approach with added correcting lenses for removal of chromatic aberration, light scattering, and increased spatial resolution in spectroscopic imaging; this approach was successfully demonstrated in applications to tissues and live cells. The presented examples also demonstrate that the actual achieved spatial resolution in FT-IR imaging is not as high as perceived by researchers using values of theoretical limits or projected pixel sizes.

	The use of discrete-frequency QCL approaches, also discussed in this article, provides an opportunity for data reduction without significant loss of achieved classification and also offers a possibility for analysis of much greater areas of samples than were previously feasible using conventional infrared sources. This approach facilitates analysis of many samples in a high-throughput manner. We have presented promising preliminary examples of the use of a QCL-based system for obtaining chemical images of esophageal biopsy, but this method can be enhanced further when combined with our correcting lens approach. Recent publications by several other research groups further demonstrate the use of such QCL system for histopathology-for example, by imaging of adenocarcinoma colorectal tissue and high-speed scanning of an entire liver biopsy (6). Furthermore, a very interesting application of QCL for high-throughput analysis of biofluids has recently been demonstrated by Matthew Baker and coworkers (7,8) and by Wrobel and Bhargava for tissue analysis (9), which provides new possibilities for medical diagnosis using such technology. Overall, these spectroscopic methods clearly have the potential to enhance our understanding of chemical changes at an intracellular level and, therefore, provide the possibility for the emergence of novel spectroscopic methodologies for enhanced diagnostics.

You have also conducted a study of Jackson Pollock's masterpiece painting 

 in which ATR-FT-IR spectroscopic imaging was used for investigation at the microscale level of the pigment–oil interaction in the painting (10). What were the main questions you were attempting to answer in this study?

	Yes, this is another exciting application of ATR-FT-IR spectroscopic imaging and I was delighted to collaborate on this research with Italian scientists from Perugia and the Peggy Guggenheim Collection in Venice on spectroscopic studies of microscopic samples from the painting by Jackson Pollock, who is described as one of the greatest figures in the abstract expressionist movement of the 20th century and has produced masterpieces using his unique technique. He routinely used a traditional oil paint (zinc oxide in linseed oil), but was unaware that this type of paint presented a potential threat to the conservation of his paintings. In this work, we applied micro ATR-FT-IR spectroscopic imaging, which we have previously used to study the degradation process of paintings from the National Gallery, London. In this work, we used this approach to detect the mechanism of detrimental formation of zinc soaps occurring inside the painting by Jackson Pollock, thus resulting in its degradation. ATR-FT-IR imaging has helped us to explain that the damage of the painting was related to the formation of zinc soaps around areas where a jellifying agent (aluminum stearate hydroxide) was present that was added in the paint formulation. This finding led to an explanation that this jellifying agent accelerated the formation of zinc soap that usually forms due to the interaction of zinc oxide with fatty acids present in the oil binder of the painting. These chemical processes were reliably assessed due to the high spatial resolution of micro ATR-FT-IR spectroscopic imaging. Previously, we used this spectroscopic approach to analyze a cross-section of hair and live cancer cells, to study atherosclerosis in arterial tissues, to investigate pharmaceutical tablets, and for many other applications.

	This spectroscopic study of Pollock's masterpiece Alchemy may help conservation scientists to preserve this, and other, important objects of cultural heritage.

In a very recent study (11), you used ATR-FT-IR spectroscopy to investigate the use of supercritical CO

 in the processing of polymeric materials in place of organic solvents. What are the advantages and possible disadvantages of using ATR-FT-IR spectroscopy for this application?

	This recent article explains why in situ ATR-FT-IR spectroscopy is a powerful method of choice for studies of polymeric materials processed with supercritical CO

. This approach was pioneered in my laboratory and has since been used by many other researchers in this field. This topic is of significant importance because it has direct implications in CO

 capture technologies and supporting the drive toward greener solvent alternatives. This article explains why supercritical CO

 is the method of choice for processing environmentally friendly materials. There are many advantages of using this ATR-FT-IR spectroscopic approach, which include chemical specificity of quantitative in situ analysis by using miniature spectroscopic cells that facilitate the use of a small amount of sample and also make these high-pressure spectroscopic experiments safer.

What are the next steps in your research with infrared spectroscopy?

	I expect to continue with other new developments in FT-IR spectroscopic imaging and their application to a broad range of novel research areas. One of our most recent research activities utilizes in situ FT-IR spectroscopy and imaging to understand key processes occurring in chromatographic columns. This work aims to reveal new insights into protein behavior during isolation, so the next steps will be made in this direction and we expect collaboration in this field with biopharmaceutical companies. I would also expect new developments into the design of new microscopes and spectrometers, such as combining the use of a QCL source with a microscope equipped with added lenses, hemispheres, or an ATR crystal, or both, for greater spatial resolution measurements that would allow the acquisition of higher quality spectroscopic images. These approaches, combined with machine learning techniques, may be applied to cancer diagnosis.

	(1) A.A. Gabrienko, O.N. Martyanov, and S.G. Kazarian, 

 4750–4757 (2016). doi: 10.1021/acs.energyfuels.6b00718.

	(2) A.V. Ewing, G.S. Clarke, and S.G. Kazarian, 

 5813–5820 (2017). doi: 10.1007/s00216-017-0574-5.

	(7) C. Hughes, G. Clemens, B. Bird, T. Dawson, K.M. Ashton, M.D. Jenkinson, A. Brodbelt, M. Weida, E. Fotheringham, M. Barre, J. Rowlette, and M.J. Baker, 

	(8) M.J. Baker, H. Byrne, J. Chalmers, P. Gardner, R. Goodacre, A. Henderson, S.G. Kazarian, F. Martin, J. Moger, N. Stone, and J. Sulé-Suso, 

(3), 1444–1463 (2018). doi: 10.1021/acs.analchem.7b05330.

	(10) F. Gabrieli, F. Rosi, A. Vichi, L. Cartechini, L.P. Buemi, S.G. Kazarian, and C. Miliani, 

 1283–1289 (2017). doi: 10.1021/acsanalchem.6b04065.

Fourier transform infrared (FT-IR) and attenuated total reflection (ATR)-FT-IR spectroscopic imaging are important tools for understanding molecular interactions. Sergei G. Kazarian of Imperial College London has used these advanced imaging techniques in a wide range of applications.

Spectroscopy-05-01-2018

Review of New Spectroscopic Instrumentation for 2018

From Heavy Metals Testing to the Measurement of Elemental Impurities in Pharmaceuticals: Over 100 Years in Making the Change

The Carbonyl Group, Part V: Carboxylates—Coming Clean

Understanding Molecular Interactions with Advanced FT-IR Spectroscopy and Imaging

Vol 33 No 5 Spectroscopy May 2018 Regular Issue PDF