Researchers Develop Water-Based Spectrophotometric Methods to Analyze Common Hypertension Drug Combination

Recently, a group of scientists at the Egyptian Russian University in Cairo developed a set of green spectrophotometric techniques capable of simultaneously quantifying two widely prescribed antihypertensive drugs, amlodipine besylate and hydrochlorothiazide, in pharmaceutical formulations, without relying on hazardous organic solvents.¹

This study, which was published in the journal Scientific Reports, introduces six validated analytical methods for resolving the two-drug binary mixture. Because amlodipine and hydrochlorothiazide are frequently co-formulated in fixed-dose combination tablets, accurate quality-control analysis of both compounds in a single preparation is a routine requirement for pharmaceutical manufacturers and regulators alike.¹

What are fixed dose drug combinations?

Fixed dose drug combinations (FDCs) take two or more active drugs and integrate them in a single tablet. These drugs are controversial, as an ongoing debate remains whether all active drugs should only be formulated as single compounds.² Normally, when FDCs are made, the only time when it is acceptable is when the dosage in each drug formulation meets the acceptable safety standards and when the combination of both drugs offers a therapeutic advantage.²

Certain criteria are used to determine whether FDCs make the most sense. These variables include whether different mechanisms activate the drugs in the combination and whether the pharmokinetics are different.²

What makes this study unique?

This study is unique because researchers developed the spectrophotometric techniques using water as the sole diluent. Conventional high-performance liquid chromatography (HPLC) and other separation-based methods commonly require acetonitrile, methanol, or other organic solvents that carry disposal and safety costs.¹ By contrast, the proposed methods exploit differences in the drugs' UV absorption profiles to achieve selectivity without solvent-intensive sample preparation.¹

How is amlodipine besylate measured?

Amlodipine besylate is measured directly from its zero-order spectrum at 366 nm. It is measured at this wavelength because this is where hydrochlorothiazide produces no measurable signal.¹ The researchers then applied five additional techniques, including dual wavelength, first derivative, ratio difference, ratio derivative, and Fourier Self-Deconvolution, to resolve hydrochlorothiazide from the mixture. Linear working ranges span 5–30 µg/mL for amlodipine and 3–18 µg/mL for hydrochlorothiazide, with limits of detection falling below 1.24 µg/mL across all six methods.¹

All procedures were validated against International Council for Harmonization (ICH) guidelines and assessed using four independent green analytical chemistry metrics, including the Analytical GREEnness Calculator and the Modified Green Analytic Procedure Index. The researchers found that all methods scored favorably on each metric.

What was the benefit of the spectrophotometric techniques developed in this study?

The authors note a specific practical advantage over earlier techniques developed for ternary drug mixtures containing a third active ingredient: those prior methods could not reliably quantify amlodipine and hydrochlorothiazide alone without the additional compound present, limiting their applicability to binary formulations common in generic manufacturing.¹

References

1. Badrawy, M.; El-Abassy, O. M.; Nour, I. M.; Eissa, A. S. Spectroscopic Methods for the Simultaneous Determination of Amlodipine Besylate and Hydrochlorothiazide in their Binary Mixture and Pharmaceutical Dosage Form. Sci. Rep. 2026, 16, 4541. DOI: 10.1038/s41598-025-33191-4
2. Gautam, C. S.; Saha, L. Fixed Dose Drug Combinations (FDCs): Rational or Irrational: A Viewpoint. Br. J. Clin. Pharmacol. 2008, 65 (5), 795–796. DOI: 10.1111/j.1365-2125.2007.03089.x