A new review has delivered a verdict that may surprise laboratory scientists who equate cutting-edge technology with best practice: when it comes to measuring two of the world’s most widely prescribed blood pressure drugs, the humblest analytical technique turns out to be the greenest. The study, published in the journal Discover Green Chemistry, systematically scored the environmental sustainability of dozens of analytical methods used to quantify amlodipine besylate and indapamide, a fixed-dose combination taken by millions of patients with hypertension. Using two established greenness assessment tools, the authors found that simple ultraviolet spectrophotometry consistently outperformed sophisticated chromatographic and mass spectrometric techniques on environmental grounds, even though those high-tech methods offer superior sensitivity.
The review’s authors, Ravi Patel of ThermoFisher Scientific, Dipen Purohit of Navinta LLC, and Krupalkumar Morker of Frontage Laboratories, compiled analytical methods published between 2010 and 2025 for the simultaneous estimation of the two antihypertensive agents in pharmaceutical formulations and biological matrices. Their motivation stems from a growing tension in pharmaceutical quality control: the same laboratories that validate drug safety generate streams of toxic solvent waste, consume large amounts of energy, and expose analysts to hazardous chemicals. As sustainability expectations rise across the industry, the environmental footprint of the analytical methods themselves has come under scrutiny alongside the performance metrics that regulators traditionally demand.
The two drugs at the center of the assessment are clinically complementary. Amlodipine besylate is a long-acting dihydropyridine calcium channel blocker that relaxes blood vessels by inhibiting calcium ion influx into vascular smooth muscle and cardiac cells, reducing peripheral resistance and the heart’s oxygen demand. Indapamide, a thiazide-like diuretic, works differently: it blocks sodium reabsorption in the kidney’s distal convoluted tubule, increasing sodium and water excretion and lowering plasma volume, while also exerting vasodilatory effects independent of its diuretic action. Combined in a single pill, the two agents achieve better blood pressure control at lower doses than either drug alone, minimizing side effects and improving patient compliance. Hypertension affects approximately 1.28 billion adults worldwide, and according to the World Health Organization nearly 46 percent of those affected are unaware of their condition, making reliable, affordable quality control for these medicines a genuine global health matter.
To quantify environmental performance, the reviewers applied two complementary scoring systems. The first, the Analytical GREEnness metric, or AGREE, was developed at Gdańsk University of Technology and evaluates a method against the twelve principles of green analytical chemistry. It produces a radial, clock-like diagram in which each segment is color-coded from red, indicating poor greenness, to green, indicating strong performance, and yields a cumulative score from 0 to 1. The second tool, the Analytical Eco-Scale, starts from an ideal score of 100 points and deducts penalty points for hazardous reagents, excessive solvent quantities, high energy consumption, waste generation, and safety risks. Methods scoring 75 or above are classified as excellent green analysis, those between 50 and 75 as acceptable, and anything below 50 as ecologically unacceptable.
The results were strikingly consistent. Spectrophotometric methods, which measure how much ultraviolet or visible light a dissolved drug absorbs, achieved AGREE scores between 0.62 and 0.66 and Eco-Scale scores as high as 97. A first derivative ratio spectrophotometry method topped the ranking with an Eco-Scale score of 97, while absorbance ratio, area under the curve, ultraviolet absorbance correction, and Vierordt’s simultaneous equations methods all clustered around AGREE scores of 0.62 to 0.66 with Eco-Scale values of 91. The reasons are straightforward: these techniques require minimal solvent, typically just methanol, need no buffer solutions, involve little or no sample preparation, consume very little energy, and generate almost no waste. For routine quality control of tablets in resource-conscious settings, the review suggests they remain hard to beat.
High-performance thin-layer chromatography, or HPTLC, produced a more nuanced picture that hinged entirely on solvent choice. A stability-indicating HPTLC method using ethanol, ethyl acetate, and triethylamine achieved the single highest AGREE score of the entire comparison, 0.70, along with an Eco-Scale score of 91, demonstrating that planar chromatography can be genuinely green when built on renewable, low-toxicity solvents. By contrast, a conventional HPTLC method relying on dichloromethane, a hazardous chlorinated solvent, scored only 0.50 on AGREE with an Eco-Scale value of 83. The lesson, the authors argue, is that the same instrumental platform can occupy opposite ends of the sustainability spectrum depending on the chemistry chosen to run it.
Conventional reversed-phase high-performance liquid chromatography, the workhorse of pharmaceutical analysis, fared less well. AGREE scores for RP-HPLC methods ranged from 0.47 to 0.61, with Eco-Scale values between 80 and 87. The environmental burden comes from the technique’s fundamental operating model: continuous pumping of mobile phase through a column at flow rates typically between 0.6 and 1.5 milliliters per minute, using organic solvents such as acetonitrile and methanol mixed with phosphate, acetate, or citrate buffers. Every analysis flushes liters of solvent mixture into waste containers over time, and the pumps and detectors draw continuous power. Methods employing phosphate buffers and triethylamine scored at the lower end of the chromatographic range, while stability-indicating variants with optimized solvent compositions achieved slightly better values.
Yet the review also identified a promising path forward within chromatography itself. An RP-HPLC method developed under Analytical Quality by Design, or AQbD, principles, using a mobile phase of methanol and 0.1 percent orthophosphoric acid at pH 4.5, reached an AGREE score of 0.61 and an Eco-Scale score of 87, among the best chromatographic results. AQbD is a systematic framework that identifies the critical method parameters affecting performance and deliberately optimizes them, and the review shows it can be steered toward environmental goals as well as analytical ones. Similarly, an eco-friendly RP-HPLC method for amlodipine impurity profiling that substituted ethanol for more problematic solvents satisfied both greenness metrics while maintaining full separation of the drug’s known impurities, and an optimized UPLC method for amlodipine recorded a low environmental impact value on the HPLC-EAT scale alongside excellent reproducibility.
At the opposite extreme sat the most technologically advanced approach. UPLC–MS/MS and LC–MS/MS methods, which couple ultra-performance liquid chromatography with tandem mass spectrometry, recorded some of the lowest scores in the assessment, with an AGREE value of 0.47 and an Eco-Scale score of 68. These hyphenated techniques are unmatched for sensitivity and specificity, capable of quantifying amlodipine, indapamide, and other antihypertensives in human serum for therapeutic drug monitoring and bioequivalence studies. But that power carries a cost: high-purity solvents, buffer salts, energy-intensive instrumentation, and complex solvent systems all weigh heavily against them on greenness metrics. The review does not suggest abandoning them, since bioanalytical work in plasma and serum has few alternatives, but it does highlight that their routine use where simpler methods suffice carries a substantial and often unexamined environmental price.
The broader message of the review extends well beyond these two drugs. Current ICH validation guidelines focus on precision, accuracy, and robustness but say little about sustainability, and the authors argue that green chemistry principles should be integrated from the earliest stages of method development rather than assessed as an afterthought. Their recommendations include replacing hazardous solvents with greener alternatives such as ethanol and ethyl acetate, minimizing solvent volumes, adopting AQbD frameworks to optimize flow rates and compositions, and pursuing miniaturization and automation. Spectrophotometric and AQbD-assisted HPTLC approaches, they conclude, offer the best combination of green credentials and analytical reliability for routine pharmaceutical quality control. As regulators and the public increasingly expect the pharmaceutical industry to align with sustainable development goals, the environmental scorecard of the laboratory bench, this review suggests, deserves the same rigor as the assay results it produces.
Subject of Research: Greenness assessment of analytical methods for quantifying amlodipine besylate and indapamide
Article Title: Comparative greenness assessment of analytical methods for the estimation of amlodipine besylate and indapamide using green analytical chemistry principles
Article References: Comparative greenness assessment of analytical methods for the estimation of amlodipine besylate and indapamide using green analytical chemistry principles. (n.d.). https://doi.org/10.1007/s44509-026-00013-3
Image Credits: AI Generated
DOI: 10.1007/s44509-026-00013-3
Keywords: green analytical chemistry, amlodipine besylate, indapamide, AGREE metric, Analytical Eco-Scale, spectrophotometry, RP-HPLC, HPTLC, UPLC-MS/MS, Analytical Quality by Design, pharmaceutical analysis, sustainability
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Bethany Barker. (September 25, 2026). Green Lab Test: Simple Spectroscopy Beats High-Tech Machines for Blood Pressure Drug Analysis. Scienmag. https://scienmag.com/green-lab-test-simple-spectroscopy-beats-high-tech-machines-for-blood-pressure-drug-analysis/
Bethany Barker. “Green Lab Test: Simple Spectroscopy Beats High-Tech Machines for Blood Pressure Drug Analysis.” Scienmag, 25 September 2026, https://scienmag.com/green-lab-test-simple-spectroscopy-beats-high-tech-machines-for-blood-pressure-drug-analysis/. Accessed 25 September 2026.
Bethany Barker. “Green Lab Test: Simple Spectroscopy Beats High-Tech Machines for Blood Pressure Drug Analysis.” Scienmag. September 25, 2026. https://scienmag.com/green-lab-test-simple-spectroscopy-beats-high-tech-machines-for-blood-pressure-drug-analysis/
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Tags: AGREE metricamlodipine besylateAnalytical Eco-ScaleAnalytical Quality by Designblood pressure drug measurement technologiescomparison of chromatography and spectrophotometryeco-friendly drug analysis for antihypertensive medicationsenvironmental impact of analytical techniquesgreen analytical chemistrygreen chemistry approaches in pharmaceutical analysisgreen spectroscopy for blood pressure drug analysisgreenness assessment of pharmaceutical quality control methodshigh-tech vs simple methods for drug testingHPTLCindapamideminimizing toxic solvent waste in labspharmaceutical analysisRP-HPLCspectrophotometrySustainabilitysustainability in analytical chemistrysustainable pharmaceutical testing methodsultraviolet spectrophotometry in drug quantificationUPLC-MS/MS
