Fadi Abou-Shakra

As the limits of detection (LODs) for trace metal analysis are increasingly being pushed to the next decimal, a need exists to meet these new detection requirements without compromising accuracy or precision. Inductively coupled plasma–mass spectroscopy (ICP-MS) is often the instrument of choice for routine applications requiring ultratrace detection limits. For a number of elements, spectroscopic interferences can have a significant impact on the ability to achieve low detection limits by traditional ICP-MS systems. In this study we take a look at multi-quadrupole ICP-MS technology, with a focus on the mechanisms of removing spectral and other interferences to secure the LODs, accuracy, and precision needed for challenging applications.

Every analytical technique has its own challenges in terms of interferences and ways to remove them. This also applies to inductively coupled plasma–mass spectroscopy (ICP-MS), which is known to have a number of well-characterized spectral interferences that are generated from matrix ions, the solvents or acids being used, and the plasma gases (1). The presence of these interferences does not only have a great impact on the limits of detection (LODs), but also affects the ability to detect and accurately quantify analytes at low concentrations. In many industries, such quantification is crucial for product safety and quality control.

Spectral interferences are typically categorized into polyatomic (including oxides and hydroxides), isobaric, and doubly-charged ionic interferences. Although sample cleanup has proven to be effective at removing a number of matrix-related spectral interferences, this approach is not popular because of the prohibitive cost and time associated with it. In some cases, it is possible to simply choose an alternative isotope that does not have an interference associated with it. However, for monoisotopic elements and those at extremely low concentrations, choosing an alternative isotope is not always a viable option. Argon-based interferences are known to be effectively lowered through the use of cold or cool plasma conditions (1, 2). Unfortunately, this approach is known to suffer from matrix (non-spectral) effects, and so its use is dependent upon the application. Consequently, ICP-MS instrumentation was developed and improved over the years to effectively reduce and eliminate a number of these interferences.

The most common way to do this is through using different modes of analysis that are possible using reaction or collision cell technology. Let’s take a detailed look at how reaction and collision cellswork compared with the more traditional ways of reducing interferences.

Principles of Reaction and Collision Cells

The use of correction equations was one of the first approaches used in ICP-MS analyses to correct for spectral interferences. Typically used to address isobaric and minor polyatomic interferences, the challenge with this approach is that it can result in overestimating or underestimating the interference, especially at lower analyte concentrations. Therefore, the use of correction equations does not always provide the level of accuracy needed. The name “standard mode” arose with the introduction of a cell before the analyzer quadrupole. In this mode of operation, the cell, though typically pressurized with a gas for other modes of operation, had no gas added, serving simply as an ion guide where correction equations were then applied to the resulting data.

The first use of a cell pressurized with gas for ICP-MS application was a radio frequency (RF)-only driven cell, which came to be known as a collision cell. 

, such as octopoles and hexapoles, are often referred to as “passive cells.” This is because these cells are not designed to have any mass separation capabilities. Instead, they were originally developed, and still continue to be used in organic mass spectrometry (tandem MS/MS), to transmit predominantly high mass ions which have resulted from the ion-fragmentation process (3). In collision mode, a non-reactive gas, such as helium, is introduced into the cell and used to pressurize it. The gas will collide with both the analyte and the polyatomic interference; however, the polyatomic ion interference typically has a larger cross-sectional diameter than the analyte ion, and will experience more collisions, lowering its kinetic energy. These polyatomic ions are then removed using a kinetic energy discrimination (KED) barrier.

This mode of operation is best used for moderate levels of interferences, and, as such, is particularly useful for the analysis of unknown matrices. The challenges associated with this mode of operation, however, are losses to analyte sensitivity and the inability to remove major interferences. For that reason, collision mode is limited to cases where the intensities of polyatomic interferences are less than four orders of magnitude higher than the analyte at that mass and where the interfering ion has a notably larger cross-sectional area than the analyte ion.

Reaction mode is typically used for applications where the interference exceeds four orders of magnitude, or where the analyte is present in extremely low concentrations, and the analysis cannot afford the signal suppression that would be introduced from a collision gas. In reaction mode, a reactive gas is introduced into the reaction cell where the choice of gas and its flow rate are selected according to reaction dynamics, which are essential for efficient interference removal. The reaction gas can either react with the interfering ion to completely remove it (exemplified in equation 1) or with the analyte ion to “mass-shift” it to a mass where there is no interference (exemplified in equation 2).

An example of using a reaction gas to remove an unwanted polyatomic interference where both the interference and the analyte ions have the same mass. In this example, 

An example of using a reaction gas to mass-shift the analyte to a new mass. In this example, 

Reaction Cell with Dynamic Bandpass Mass Tuning

One of the many concerns with conventional reaction cells is that byproducts of the chemical reactions can react with the reaction gas and other ions in the cell to form new interferences. When this happens, passive cells only have limited applicability, and this is where active cells have become extremely useful. Owing to their mass filtering capabilities, quadrupole-based collision–reaction cells can be used to eject reaction by-products before they have a chance to react and form new interferences. This approach, called 

 (Universal Cell Technology), provides a clear advantage over higher order multipoles which lack the mass filtering capability to control these byproduct side reactions.

Further Reduction of Spectral Interferences

However, there are other complementary ways of reducing polyatomic and isobaric spectral interferences in ICP-MS, with the use of additional mass separation devices. Let’s take a closer look at some of these approaches.

Most ICP-MS instruments have a number of ion lenses that are used to filter the ion beam of unwanted photons and neutral species before they enter the cell. Historically, these lenses were designed in tandem with the interface cones. In 2010, however, the quadrupole ion deflector (QID) was developed (PerkinElmer Inc.), where an additional quadrupole was placed directly after the cones, replacing the traditional lens system. The role of this quadrupole was to deflect the ion beam 90°, while the photons and neutral species remain unaffected by the applied voltage and are removed via the vacuum. A benefit of this technology is that it behaves as an electrostatic analyzer that reduces the kinetic energy spread of the ions, and can operate with either a fixed or variable quadrupole voltage.

With a fixed voltage, a mass range of interest around the analyte ion can be transmitted to the cell, whereas ions outside this mass range are filtered off. This reduces matrix loading onto the cell or first quadrupole (depending on the instrumentation being used), and lowers the chances of new interferences forming in the cell from matrix ions. A good example of this would be for zinc (Zn), which would typically be reacted with NH

) at mass 115. By fixing the voltage of the QID to the mass window around mass 64, 

 ions, if present in the sample, are diverted away from the cell. As a result, a better S/N ratio for the zinc cluster ion at mass 115 is achieved.

An alternative approach to reducing interferences is to use a traditional triple quadrupole design whereby a passive cell (Q2) is placed between two quadrupole mass spectrometers. This approach, popular in organic mass spectrometry, where parent ions are subjected to collisional induced dissociation in the cell, was commercially adopted for ICP-MS in 2012. This design allows the analyst to select only the nominal mass of interest in the first analyzer quadrupole, eliminating other masses from the ion beam so that only the analyte and interfering ions remain. The interference is then removed through the use of reaction chemistry, and sometimes KED, in the collision–reaction cell (Q2), which allows the analyte to be separated from the interference in the final analyzer quadrupole. One limitation of this approach is that the cell is passive, and therefore offers no control over any potential side reactions between the reaction by-products and the gas itself or impurities in the cell gas.

In a multi-quadrupole design, the passive cell of traditional triple quadrupole designs is replaced with an active cell possessing mass filtering capabilities. Such cells can operate in either passive (triple quadrupole) or active (multi-quadrupole) modes, and offers the ability to reject the reaction byproducts before they can potentially generate any new interferences. Figure 1 shows the layout configuration of the four quadrupoles.

This design allows the ion beam to be cleaned up in the first quadrupole (Q0), followed by mass selection in the first transmission analyzer quadrupole (Q1),removing all interferences which are not at the desired nominal mass. After this, the analyte and any interferences that are at the same nominal mass are introduced into the active quadrupole cell (Q2) where the dynamic bandpass mass tuning capability of the cell effectively eliminates reaction byproducts before they have a chance to form new interferences. Thereafter, the interfering and analyte ions are efficiently separated in the final transmission analyzer quadrupole (Q3) in a manner that depends on the mode of operation (MS/MS or mass-shift). In this way, it not only controls the ions that enter the cell, but also controls the reactions within the cell, ensuring that byproduct ions are not formed.

Let’s explore the fundamental differences between a conventional triple quadrupole system and the multi-quadrupole technology by highlighting the determination of chromium in an organic solvent, which is particularly difficult using a passive collision–reaction cell. Note that the data in this example and all subsequent data have been generated on a NexION 5000 ICP-MS system (PerkinElmer Inc.) (4).

Detection limits for chromium tend to be poor in organic matrices because of the 

C polyatomic interference that forms as a result of the plasma gas and organic solvent. Figure 2 shows a product ion scan of 1% methanol, where Q1 was set to mass 52 and Q3 was set to scan the mass region from 4 to 100 amu with an NH

 gas flow of 1 mL/min. Pure ammonia was used for this reaction because it is known to produce highly efficient and reproducible reactions. In order to duplicate a passive collision cell (triple quadrupole mode), a rejection parameter q (RPq) value of 0.05 was used. Four peaks can be clearly observed at masses 18, 19, 35, and 52 (

 ions respectively. The presence of these ions was confirmed by peaks at masses 18 and 19, whose abundance has the same relationship as the two isotopes of nitrogen (shown in Table I) as was determined using the formula shown in equation 3. Also contributing to the peak at mass 52 are chromium impurities in the methanol, as a result of the methanol HPLC gradient grade being used (≥ 99.8% HiPerSolv Chromanorm, VWR Chemicals BDH).

As evidenced in Figure 2, it can be clearly observed that additional species have formed from the NH

 in the cell, even though only mass 52 was allowed through Q1 and the 

C interference was removed via the reaction mode. However, once dynamic bandpass mass tuning was applied by increasing the RPq (shown in Figure 3), it can be clearly seen that all peaks that had been generated from the reaction gas are completely eliminated, leaving behind a clean and significantly smaller peak (ca. 500 cps) at mass 52, which equates to ~5 ppt Cr impurity, which could be due to the fact that methanol has been traditionally stored in stainless steel containers.

By plotting the background equivalent concentrations (BECs) against the RPq, the benefits of an active cell are apparent, as exemplified in Figure 4. Operating in “triple quad mode” at an RPq of 0.05, the BEC was around 966.7 ppt. By using the power of dynamic bandpass mass tuning a significant lowering of the BEC down to 5 ppt can be clearly observed.

Figure 4 highlights why, despite the effective way that triple quadrupole designs deal with interferences, it is challenging for these systems to reach sub-1 ppt BECs for some elements using hot plasma conditions. However, with the use of multi-quadrupole technology, BECs of <1 ppt in a hot plasma can easily be achieved.

Let’s take a more detailed look at two very important application segments for ICP-MS where ultra-low detection capability and interference reduction is critically important—semiconductor and biological applications.

As can be expected, the cleanliness of chemicals in the semiconductor industry is critical to guaranteeing the quality and improved yields of semiconductor products (7). Ultrapure water is one such chemical and is used in a variety of different processes throughout this industry. For this reason, the Semiconductor Equipment and Materials International (SEMI F63-0918) (5) and American Society for Testing and Materials International (ASTM D5127-13) (6) have developed standards associated with the production and point of delivery of ultrapure water. The SEMI F63-0918 “Guide for Ultrapure Water Used in Semiconductor Processing,” for example, has set a target value of <1 ppt for the maximum allowable concentrations of 26 metallic contaminants with the exception of boron (50 ppt) and nickel (3 ppt).

As described by Pruszkowski (7), using the multi-quadrupole ICP-MS instrument in hot plasma mode and 100% NH

 (depending upon the analyte) as reaction gases, the detection limits for all 26 elements essential to the semiconductor industry were found to be <0.3 ppt (shown in Figure 5), easily satisfying the 1 ppt requirement of SEMI and ASTM standards (7). The BECs for most of these elements were in fact found to be less than 0.5 ppt and as such demonstrates the efficiency of spectral interference removal (7).

Another application area where accuracy at low levels is extremely important is in the measurement of trace metals in whole blood and serum. Blood is a complex mixture of water, red and white blood cells, proteins, hormones, glucose, and mineral salts (8). Serum is derived from blood via centrifugation, and has a similar composition despite lacking in red and white blood cells and fibrinogens (8). Aside from being a very complex mixture, blood panels are typically run to make decisions about the health of the patient where sometimes the presence of extremely low concentrations of the metal in the patient can lead to adverse effects, hence the need for good accuracy with low method detection limits (8). As described by Pruszkowski (8), Figure 6 demonstrates that, despite the complex matrix of the blood samples and diluent being used (1% HNO

 + 0.05% Triton X), extremely low MDLs were achieved (Note: MDLs were determined by analyzing the diluent 7x, and the resulting standard deviations multiplied by 50 (the dilution factor) and 3.14 (99% confidence limit)) (8).

To demonstrate the accuracy of this methodology, ClinChek Levels I, II, and III whole blood control standards were analyzed using the same sample preparation procedure and comparing them against calibration curves prepared by 50x, 100x, and 200x dilutions of a ClinCal calibration standard (8). The results in Table II show percent recoveries compared to the normalized results of the mean certificate values. It can be seen that recoveries are well within the certified values (8).

In conclusion, multi-quadrupole ICP-MS technology offers a distinct advantage over traditional approaches in the removal of spectral interferences, by not only controlling the ions that enter the cell, but also the reaction products within the cell. For example, there is an improvement of approximately two orders of magnitude in the background equivalent concentrations when the bandpass is applied for chromium, which has a direct impact on the detection limit. This allows for the accurate sub-ppt quantification of analytes in the semiconductor industry even in the hot plasma mode, which does not suffer from the same non-spectral matrix effects as are often observed when using cold plasma conditions. Furthermore, this technology can be extremely useful in the field of biomonitoring studies, effectively removing the spectral interferences to provide high accuracy at low levels in complex sample matrices. The application of this technology is not limited to these application fields, but can be extended to other applications where spectral interferences are a significant limitation such as environmental, geochemical, petrochemical, and academic research.

 (Marcel Dekker Inc., New York, New York, 2004).

PerkinElmer. NexION 5000 ICP-MS Product Technical Note. 

https://www.perkinelmer.com/Product/nexion-5000-icp-ms-n8160010

ASTM D5127-13. Standard Guide for Ultra-Pure Water Used in the Electronics and Semiconductor Industries. 

SEMI F63-0918. Guide for ultrapure water used in semiconductor processing. 

https://store-us.semi.org/products/f06300-semi-f63-guide-for-ultrapure-water-used-in-semiconductor-processing

E. Pruszkowski, PerkinElmer Application Note: Characterization of Ultrapure Water using NexION 5000 ICP-MS. 

https://www.perkinelmer.com/lab-solutions/resources/docs/APP_Nexion5000-ICP-MS-SemiconUltrapureWater.pdf

E.Pruszkowski, PerkinElmer Application Note: Analysis of Blood using NexION 5000 ICP-MS. 

https://www.perkinelmer.com/lab-solutions/resources/docs/app_nexion5000-icp-ms-biomonitoringblood.pdf

 is an Associate Product Leader for ICP-MS at PerkinElmer, Inc.

is the Portfolio Director for ICP-MS at PerkinElmer, Inc.

is the principal of Scientific Solutions, an educational consulting company that serves the training and writing needs of the trace element user community. He has worked in the field of atomic and mass spectroscopy for more than 45 years, including 24 years for a manufacturer of atomic spectroscopic instrumentation. Rob has written more than 100 scientific publications, including a 15-part tutorial series, A Beginners Guide to ICP-MS. He is also the editor and frequent contributor of the Atomic Perspectives column in 

 magazine. In addition, Rob has authored three textbooks on ICP-MS and in 2018 completed his fourth book, entitled 

Measuring Elemental Impurities in Pharmaceuticals

. He has spent the past two years researching and writing a new book, 

Measuring Heavy Metal Contaminants in Cannabis and Hemp,

 which was published in September 2020. Rob 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).

Articles

For a number of elements, spectroscopic interferences can have a significant impact on the ability to achieve low detection limits in ICP-MS. We investigate the mechanisms in multi-quadrupole ICP-MS that are designed to remove these interferences.

Multi-Quadrupole ICP-MS: Pushing Limits of Detection to the Next Decimal

To address the challenges associated with a broad, complicated food and beverage supply chain, innovative solutions for contaminant detection are continually being sought. Easy-to-operate instrumentation and methodology can be adopted over the entire food supply chain, allowing contaminated food samples to be identified more readily. Here, we describe a simple method capable of identifying and quantifying a diverse range of elements, including trace metals that are toxic in low concentrations, and also the major elements that are essential to healthy sustainable life. Inductively coupled plasma mass spectrometry (ICP

MS) is the definitive technique used to identify and quantify potential metal contaminants; here it has been applied to the metals present in samples of milk powder and evaporated or condensed milk. The ICP

MS method used enabled the detection of metals with quantitation limits to the order of parts per billion. It was found that all milk samples contained elemental concentrations below those levels directed by regulation, with milk powders containing the highest concentrations of major metal elements.

	Mass spectrometry has increasingly become associated with the detection of contaminants and nutrients in food, overtaking other less common methods of detection. Under the umbrella of mass spectrometry are inductively coupled plasma mass spectrometry (ICP-MS) and liquid chromatography and tandem mass spectrometry (LC–MS/MS), which have both been adopted increasingly by researchers throughout the world to identify and quantify contaminants and nutrients in food. As demonstrated by the 2017 fipronil contamination scare (1), there is an industrial necessity to provide reliable analysis methods that can be applied by any food scientist within any processing facility. In tandem with the detection of contaminants, food must also be nutritious, supplying consumers with the essential components of life, such as the metals that are involved in important biological processes.

	Elements are the building blocks of life, and we need to ensure that we receive the right mixture of elements at the appropriate dosage for our continued sustainable development and healthy growth. Of the 118 elements on the periodic table, the majority are metals. For humans, receiving the appropriate levels of certain metals is vital to our existence. Iron, for instance, is an essential component of hemoglobin, and assists in transporting oxygen throughout the body. Other major elements include sodium, potassium, magnesium, copper, and zinc, all of which facilitate a range of biological functions and roles within the human body, making them nutritionally essential. Therefore, in order to function appropriately, we need to be sure we are accumulating the right mixture of elements at the appropriate levels. Dosage of any element is important; an element must be present at a safe enough level to provide functionality, but not so high that it becomes toxic. This means reliable quantitation is essential.

	However, there are also those elements that are toxic even in low concentrations. For instance, the metalloid arsenic (2), and heavy metals such as mercury (3), lead (4), and cadmium (5) have been associated with a variety of health issues. While heavy metals occur naturally, their release into the environment is often a result of anthropogenic activities that are commonly industrially related (6), which can facilitate their dispersion into the food chain. To address the variety of health issues associated with heavy metal contamination, government or independent health experts have imposed maximum levels of metals in foodstuffs to further protect the public.

	ICP-MS itself is becoming renowned as the method of choice for metal analysis across a variety of applications from pharmaceutical development and cancer research (7) to environmental and food analysis (8,9). Specifically considering its use in the food industry, ICP-MS has been used across a variety of applications such as arsenic detection in rice (10). One of the specialties of ICP-MS is its intrinsic use of plasma that completely ionizes the entire sample, ensuring the detection of all metals or analytes. Methods such as atomic absorption spectroscopy and ICP-OES have been successfully applied to the analysis of metal elements within samples of food (11). However, both these methods lack either the multi-element detection capabilities or the sensitivity that ICP-MS offers.

	For food samples, the ability to identify and quantify the various metal elements within a given sample is essential both for contaminant detection and accurate nutrient reporting. Here, we describe a fast and simple method capable of detecting a dynamic range of elements to a high level of reliability and accuracy within various samples of milk with variable fat levels. Milk is well known as a source of nutrition in the early development of children. During these early stages, confidently knowing the quantities of nutritional elements being ingested is critical to healthy growth. This underpins the need for a useful methodology that can provide simple solutions to food scientists across the globe (12).

	Six samples of milk were purchased from local stores for analysis. Samples were chosen to provide a concise coverage of various types of milk with a varied concentration of fat. The forms of milk used were: skimmed milk powder (non-fat), light evaporated milk (4% fat), evaporated milk (9% fat), sweetened condensed milk, skimmed milk (ultra-high temperature (UHT) milk, <0.5% fat), and semi-skimmed milk (UHT, < 2% fat). For experimental controls, three certified reference materials were also obtained. Two European Reference Materials (ERMs) were obtained from the Joint Research Centre of the European Commission, denoted as ERM-BD 150 and ERM-BD 151. The National Measurement Institute of Japan (NMIJ) sample, NMIJ 7512-a, was obtained from GL Sciences B.V.

	Milk samples of varying weights (5 g of UHT milk, 2 g evaporated milk, 1 g condensed milk, and 0.5 g milk powder) were digested with a combination of concentrated 2.5 mL nitric acid (Fluka, TraceSelect Ultra) and 2.5 mL 30% hydrogen peroxide (Sigma-Aldrich, H

 ≥30%, for Ultratrace analysis). Samples were made up to equivalent volume by the addition of water, which was altered to account for the varying concentrations in the different types of milk (0 mL for UHT milk, 3 mL for evaporated milk, 4 mL for condensed milk, and 5 mL for milk powder). Samples were then heated using a Titan MPS Microwave Sample Preparation System using standard 75 mL vessels. Digests were transferred to 50 mL autosample tubes and spiked with 10 µL of 1000 mg/L gold solution before being made up to 50 mL with deionized water.

	Analyses were performed using the NexIon 2000 P ICP-MS instrument (PerkinElmer) with sample detection achieved using a collision mode to reduce elemental interference. The technical parameters for the instrument are reported in Table I. No modifications were made to the instrument and the default sample introduction system was used.

Detection of Major and Trace Elements in Milk Samples

	Before we discuss the analysis of store-bought milk samples in detail, the methodology of sample preparation and comparisons between the control and current methods should be explained in further detail. The first important step in preparing samples for analysis is the removal of the fat content. Milk samples vary in the quantity of fats. For instance, skimmed milk powder is considered to contain no fat, whereas evaporated milk typically contains 9% fat. Excess fat in the samples will negatively affect the performance of the ICP-MS. Therefore, excess fat must be broken down prior to sample analyses to ensure quality and consistency between samples and the uninhibited detection of the elements.

	To break down fats, the sample is digested. While there are several conceivable methods of achieving this, the method employed here involves a mixture of nitric acid and hydrogen peroxide. This mixture breaks down the proteins and makes the sample more viscous. It is then necessary to heat samples, which facilitates digestion. The method used here involves the use of a microwave to ensure uniform heating across the entire sample. An alternative could involve using heating blocks, however, this might result in uneven heating.

	Following digestion, the certified reference materials are analyzed to demonstrate the accuracy of the methodology being used. The results of NMIJ 7512-a milk powder sample and ERM-BD 150 and ERM-BD 151 skimmed milk powders are reported in Tables II and III, respectively. Recovery rates (the difference between the measured and certified samples) are in the range of 89–107%, 93–105%, and 94–99% for the three CRM samples, respectively. These excellent recovery rates demonstrate an overall agreement between the control experimental levels and the presently employed methodology, meaning we can be confident in the elemental breakdown of the milk samples.

	Next, the limits of quantitation (LOQ) must be discussed further. These limits are essential in order to identify the limitations of the instrumentation and determine whether results obtained are trustworthy. The limits of UHT milk samples were calculated following recommendations of the Commission Regulation (EC) No 333/2007 (13) as 10 times the standard deviation of 10 consecutive blank measurements. Milk powder LOQs were taken as 100 times the limit of the UHT samples.

	One of the challenges of using ICP-MS is in the potential for the interference of elements that can lead to false positive element detection. This is a common issue, and is the result of cross-reactivity between various other species. For instance, 

Fe (14). In this example, to prevent false detection of iron, the argon oxide analyte needs to be removed. This is where collision cells become useful. Collision cells work on the principle that the interfering ion, in this case ArO

, is much larger than the analyte, in this case Fe

. Upon ionization, both species travel through a stream of inert gas. The larger analytes are more likely to collide with gas particles that remove them from the mass spectrometer instrument. The intensity of all analytes is reduced, including the desired analyte as a result of a low proportion of collisions with the inert gas stream. However, any analyte intensity reduction is offset by the reduction in the intensity of the interference.

	Analytes of any form are then compared against regulation approved levels to ensure that the food is safe. Levels of specific metals must be within defined limits, typically sub parts per million. As defined by the Commission Regulation (EC) 1881/2006, the regulated levels for lead and tin in milk are 0.02 and 50 mg/kg, respectively (15). In this instance, it was possible to detect metals to the level of singular parts per billion, well below the relevant limits. The measured LOQs for lead and tin in milk powders are 0.0017 and 0.012 mg/kg, respectively, several orders of magnitude below the limits. In addition, the LOQ for mercury was found to be 0.0083 mg/kg, indicating the potential to detect ultralow levels of mercury in milk. LOQs to this order of magnitude below the regulatory limits add credence and confidence to the results of the experiment.

	Using the methodology outlined in the experimental section, the store-bought samples were analyzed to identify and quantity a range of elements. This included the so-called essential major elements such as sodium, magnesium and calcium, amongst others, and also the toxic trace elements such as mercury, cadmium and lead. Measured concentrations for the various samples of milk are reported in Figure 1. Any sample with a reported measurement below the LOQ has not been plotted.


	Figure 1: Results of analysis for store-bought samples (milk powder in black; evaporated milks in shades of orange; UHT milks in shades of blue-grey). Values below the LOQ have not been plotted.

	From Figure 1, it is clear that the concentrations of major elements are highest in milk powder samples, followed by condensed and evaporated milk samples and finally are lowest in the UHT samples. Certain spikes in samples can potentially be explained as a result of the storage method of the milk. For instance, the elevated levels of tin in evaporated and condensed milk have been hypothesized to be a result of their storage in tin-steel cans. This phenomenon is not unique to milk, and in fact has previously been detected in other examples of canned foods (16).

	Fundamentally, this method offers an advantageous analytical technique for the analysis of metal elements over previous instrumentation and methodology due to its twofold advantages. First, it presents a simple method to reliably quantitate a dynamic range of elements that include both trace toxic metals and those essential for health and well-being within milk samples. Secondly, it demonstrates the ability to implement a relatively simple methodology for the employment of metals detection.

	This method provides an analytical technique for the analysis of metal elements in milk demonstrating a twofold advantage. First, it provides a simple method for quantitative analysis over a wide dynamic range of elements, including both toxic metals and those metals essential for health and well-being. Secondly, it demonstrates a simple methodology for a wide spectrum detection of metals.

	(1) European Commission Fipronil Factsheet, 2017, available at: 

https://ec.europa.eu/jrc/en/publication/brochures-leaflets/fipronil-eggs-factsheet-december-2017

https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2009.1351

https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2004.34

https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2010.1570

	(7) E.M. Brouwers, M. Tibben, H. Rosing, J.H.M. Schellens and J.H. Beijnen, 

http://aaes.auburn.edu/wrc/wp-content/uploads/sites/108/2015/11/ICP-MS-review-.pdf

	(9) The Analysis of Food Substances by ICP-MS, 2008 

http://www.spectroscopyonline.com/analysis-food-substances-icp-ms

	(10) PerkinElmer application note, Arsenic Speciation Analysis in White Rice by HPLC/ICP-MS Using the NexION 300D/350D, 2014, available through the following link: 

http://www.perkinelmer.co.uk/lab-solutions/resources/docs/NexION300D-ArsenicSpeciationInWhiteRice.pdf

	(11) PerkinElmer application note, Determination of Lead and Cadmium in Foods by Graphite Furnace Atomic Absorption Spectroscopy, 2014, available through the following link: 

http://www.perkinelmer.co.uk/lab-solutions/resources/docs/APP_PinAAcle-900H-Lead-Cadmium-in-Food-011965_01.pdf

	(12) R. Pilarczyk, J. Wójcik, P. Czerniak, P. Sablik, B. Pilarczyk and A. Tomza-Marciniak, 

	(13) Commission Regulation (EC) No 333/2006, Laying down the Methods of Sampling and Analysis for the Official Control of the levels of Lead, Cadmium, Mercury, Inorganic Tin, 3-MCPD and benzo(a)pyrene in Foodstuffs, Official Journal of the European Union, European Commission, 2007, L 88, 29 

https://eur-lex.europa.eu/legal-content/EN/TXT/?qid=1529508094989&uri=CELEX:32007R0333

	(14) PerkinElmer technical note, The 30 minute guide to ICP-MS, available through the following link: 

https://www.perkinelmer.com/lab-solutions/resources/docs/TCH-30-Minute-Guide-to-ICP-MS-006355G_01.pdf

	(15) Commission Regulation (EC) No 1881/2006, Setting Maximum Levels for Certain Contaminants in Foodstuffs, Official Journal of the European Union, European Commission, 2006, L 364, 5 

https://eur-lex.europa.eu/legal-content/EN/TXT/?qid=1529507427510&uri=CELEX:02006R1881-20170728

is an inorganic field application specialist at PerkinElmer, in Milan, Italy. 

 is the ICP-MS portfolio director at PerkinElmer in Toronto, Ontario, Canada. Direct correspondence to: 

The method described here is a simple method for detection of a wide spectrum of metals and for quantitative analysis over a wide dynamic range of elements, including both toxic metals and those metals essential for health and well-being.

Fadi Abou-Shakra

Articles

Multi-Quadrupole ICP-MS: Pushing Limits of Detection to the Next Decimal

A Simple and Effective ICP-MS Method Capable of Detecting Trace and Major Elements in Milk Samples