GREEN ANALYTICAL CHEMISTRY IN PHARMACEUTICAL METHOD DEVELOPMENT: SUSTAINABLE APPROACHES

Kiran Kumar Byram; Sagar  Patel; Chirag Patel; Rasheed Babu Shaik; Shravan Kumar Muthyam

doi:10.47957/ijpda.v14i2.721

Authors

Kiran Kumar Byram Department of Chemistry, Acharya Nagarjuna University, NH 16, Nagarjuna Nagar, Guntur, Andhra Pradesh 522510
Sagar Patel Research Scientist II, Department of AR&D, Amneal Pharmaceuticals, 49 Colonial Drive, Piscataway, New Jersey 08854
Chirag Patel Senior scientist, Department of AR&D, Amneal Pharmaceuticals, 49 Colonial Drive, Piscataway, New Jersey 08854
Rasheed Babu Shaik Analytical Scientist-III, AR&D Medpharm manufacturing service’s LLC 4018 Stirrup Creek Dr, Durham, NC 27703, US
Shravan Kumar Muthyam Lead Scientist, Quality Control, New England Avenue, Piscataway, NJ, 08854.

DOI:

https://doi.org/10.47957/ijpda.v14i2.721

Keywords:

Green Analytical Chemistry, Pharmaceutical analysis, Green solvents, Sustainable methods, HPLC, GAPI, AGREE

Abstract

Green Analytical Chemistry (GAC) has emerged as a sustainable approach in pharmaceutical method development, aiming to minimise environmental impact while maintaining analytical efficiency and reliability. Conventional analytical techniques often rely on toxic solvents, high energy consumption, and generate significant chemical waste, necessitating the adoption of greener alternatives. This review highlights the principles of GAC, including reduction of hazardous reagents, minimisation of solvent use, energy efficiency, waste management, and the use of renewable materials. The application of green solvents such as water, ethanol, supercritical CO?, ionic liquids, and deep eutectic solvents is discussed. Various green analytical techniques, including green HPLC, UPLC, SFC, spectroscopic methods, electroanalytical techniques, and microextraction approaches, are explored for sustainable pharmaceutical analysis. Additionally, green sample preparation methods and evaluation tools such as Analytical Eco-Scale, GAPI, and AGREE are emphasised for assessing method greenness. Despite significant advancements, challenges such as limited green alternatives, validation complexities, and cost constraints remain. The integration of green principles with modern analytical technologies is essential for achieving environmentally sustainable pharmaceutical practices.

Armenta S, Garrigues S, de la Guardia M. Green analytical chemistry. TrAC Trends Anal Chem. 2008;27(6):497–511.
Ga?uszka A, Migaszewski Z, Namie?nik J. The 12 principles of green analytical chemistry and the significance mnemonic of green analytical practices. TrAC Trends Anal Chem. 2013;50:78–84.
Tobiszewski M, Mechli?ska A, Namie?nik J. Green analytical chemistry in sample preparation for determination of trace organic pollutants. TrAC Trends Anal Chem. 2009;28(8):943–951.
P?otka-Wasylka J. A new tool for the evaluation of the analytical procedure: Green Analytical Procedure Index. Talanta. 2018;181:204–209.
Pena-Pereira F, Tobiszewski M. The principles of green analytical chemistry and their application in sample preparation. Anal Methods. 2017;9:1–14.
Koel M, Kaljurand M. Application of the principles of green chemistry in analytical chemistry. Pure Appl Chem. 2006;78(11):1993–2002.
Namie?nik J. Trends in environmental analytics and monitoring. Crit Rev Anal Chem. 2002;32(1):1–9.
Anastas PT, Warner JC. Green Chemistry: Theory and Practice. New York: Oxford University Press; 1998.
Kümmerer K. Sustainable from the very beginning: rational design of molecules by life cycle engineering as an important approach for green pharmacy and green chemistry. Green Chem. 2007;9:899–907.
Capello C, Fischer U, Hungerbühler K. What is a green solvent? A comprehensive framework for the environmental assessment of solvents. Green Chem. 2007;9:927–934.
Byrne FP, Jin S, Paggiola G, Petchey THM, Clark JH, Farmer TJ, et al. Tools and techniques for solvent selection: green solvent selection guides. Sustain Chem Process. 2016;4:7.
Herrero M, Cifuentes A, Ibáñez E. Sub- and supercritical fluid extraction of functional ingredients from different natural sources. J Chromatogr A. 2006;1112(1–2):63–75.
Tang B, Row KH. Recent developments in deep eutectic solvents in chemical sciences. Monatsh Chem. 2013;144:1427–1454.
Pena-Pereira F, Namie?nik J. Ionic liquids and deep eutectic mixtures: sustainable solvents for extraction processes. ChemSusChem. 2014;7(7):1784–1800.
Cvjetko Bubalo M, Vidovi? S, Radoj?i? Redovnikovi? I, Joki? S. Green solvents for green technologies. J Chem Technol Biotechnol. 2015;90(9):1631–1639.
Kerton FM, Marriott R. Alternative Solvents for Green Chemistry. 2nd ed. Cambridge: Royal Society of Chemistry; 2013.
Chemat F, Vian MA, Cravotto G. Green extraction of natural products: concept and principles. Int J Mol Sci. 2012;13(7):8615–8627.
Buszewski B, Szultka M. Past, present, and future of solid phase extraction: a review. Crit Rev Anal Chem. 2012;42(3):198–213.
Kataoka H. New trends in sample preparation for clinical and pharmaceutical analysis. TrAC Trends Anal Chem. 2003;22(4):232–244.
Majors RE. Ultra-high-pressure liquid chromatography: faster, better, greener. LC GC Eur. 2005;18:8–14.Lesellier E, West C. The many faces of packed column supercritical fluid chromatography—a critical review. J Chromatogr A. 2015;1382:2–46.
Wang J. Electrochemical detection for microscale analytical systems: a review. Talanta. 2002;56(2):223–231.
Lord H, Pawliszyn J. Evolution of solid-phase microextraction technology. J Chromatogr A. 2000;885(1–2):153–193.
Reyes DR, Iossifidis D, Auroux PA, Manz A. Micro total analysis systems. Anal Chem. 2002;74(12):2623–2636.
Murali Krishnam Raju P, Shyamala P, Venkata Narayana B, Dantuluri HSNR, Bhupatiraju RV. A fast, validated UPLC method coupled with PDA-QDa detectors for impurity profiling in betamethasone acetate and betamethasone phosphate injectable suspension and isolation, identification, characterization of two thermal impurities. Annales Pharmaceutiques Françaises. 2022 Nov;80(6):837–52.
Kaufmann B, Christen P. Recent extraction techniques for natural products: microwave-assisted extraction and pressurized solvent extraction. Phytochem Anal. 2002;13(2):105–113.
Keith LH, Gron LU, Young JL. Green analytical methodologies. Chem Rev. 2007;107(6):2695–2708.
Kralisch D, Ott D, Gericke D. Rules and benefits of life cycle assessment in green chemical process and synthesis design. Green Chem. 2015;17:123–145.
Mohan Kk, Patrudu Tb, Burle Gs, Salakolusu S, Raju Pvn, Jonnalagadda Sb, et al. Isolation and structural elucidation of an unknown novel impurity in sulfasalazine by high-performance liquid chromatography coupled to mass spectroscopy and toxicology prediction. Chinese Journal of Analytical Chemistry [Internet]. 2025 Jul 19;53(11):100601.
T.K. Reddy, G. Surendra, E.J. Mart, R.H. Babu, M.S. Arabath S.A., P. Erukulla, K.V. Kandimalla, P.V.N. Raju, Computational Identification of Natural Product–Based Aryl Hydrocarbon Receptor Modulators for Psoriasis Therapy. Chem. Methodol., 2026, 10(4) 450-464
Erukulla, P.V. Narasimha Raju, K.T. Kumar Reddy, V.R. Singamaneni, A. Pathak, S. Kumar Yadav, M. Sandeep Kumar,A.A. Mohathasim Billah. Emerging Analytical Techniques for Detection of Environmental Pollutants: A Review. Adv. J.Chem. A, 2026, 9(6), 962-996.
Hechhu, K. Krishnan, V. Singamaneni, P.V.N. Raju, P. Erukulla, K.V. Kandimalla, R.H. Babu, N. Vidiyala, GC-MS-Based Phytochemical Analysis, In-depth ADMET Screening and Molecular Docking Targeting EGFR for Anticancer Potential, Chem. Methodol., 2026, 10(5) 465-488
M. Bairagi, J.G. Wagh, A.R. Thanage, P. Venkata Narasimha Raju, P. Erukulla, K. Vamsi Kandimalla, A. Manukonda, R. Hari Babu. Green Extraction, Antioxidant, and Hepatoprotective Evaluation of Calotropis procera Leaf Extract. Asian Journal of Green Chemistry, 10 (3) 2026, 430-449.
Bonu P, B C, A HVS, M D, B A. RP-HPLC Method Development and Validation for the Simultaneous Determination of Candesartan cilexitil and Hydrochlorothiazide. Journal of Innovations in Applied Pharmaceutical Science (JIAPS). 2026 Apr 13;33–6.
M PE. advances in chromatographic and spectroscopic characterization of blue pea pigments and phenolics. Journal of Innovations in Applied Pharmaceutical Science (JIAPS). 2026 Feb 27;7–12.
Lapkin AA, Constable DJC. Green Chemistry Metrics: Measuring and Monitoring Sustainable Processes. Oxford: Wiley-Blackwell; 2008.

Downloads

Download data is not yet available.

References

Armenta S, Garrigues S, de la Guardia M. Green analytical chemistry. TrAC Trends Anal Chem. 2008;27(6):497–511.

Ga?uszka A, Migaszewski Z, Namie?nik J. The 12 principles of green analytical chemistry and the significance mnemonic of green analytical practices. TrAC Trends Anal Chem. 2013;50:78–84.

Tobiszewski M, Mechli?ska A, Namie?nik J. Green analytical chemistry in sample preparation for determination of trace organic pollutants. TrAC Trends Anal Chem. 2009;28(8):943–951.

P?otka-Wasylka J. A new tool for the evaluation of the analytical procedure: Green Analytical Procedure Index. Talanta. 2018;181:204–209.

Pena-Pereira F, Tobiszewski M. The principles of green analytical chemistry and their application in sample preparation. Anal Methods. 2017;9:1–14.

Koel M, Kaljurand M. Application of the principles of green chemistry in analytical chemistry. Pure Appl Chem. 2006;78(11):1993–2002.

Namie?nik J. Trends in environmental analytics and monitoring. Crit Rev Anal Chem. 2002;32(1):1–9.

Anastas PT, Warner JC. Green Chemistry: Theory and Practice. New York: Oxford University Press; 1998.

Kümmerer K. Sustainable from the very beginning: rational design of molecules by life cycle engineering as an important approach for green pharmacy and green chemistry. Green Chem. 2007;9:899–907.

Capello C, Fischer U, Hungerbühler K. What is a green solvent? A comprehensive framework for the environmental assessment of solvents. Green Chem. 2007;9:927–934.

Byrne FP, Jin S, Paggiola G, Petchey THM, Clark JH, Farmer TJ, et al. Tools and techniques for solvent selection: green solvent selection guides. Sustain Chem Process. 2016;4:7.

Herrero M, Cifuentes A, Ibáñez E. Sub- and supercritical fluid extraction of functional ingredients from different natural sources. J Chromatogr A. 2006;1112(1–2):63–75.

Tang B, Row KH. Recent developments in deep eutectic solvents in chemical sciences. Monatsh Chem. 2013;144:1427–1454.

Pena-Pereira F, Namie?nik J. Ionic liquids and deep eutectic mixtures: sustainable solvents for extraction processes. ChemSusChem. 2014;7(7):1784–1800.

Cvjetko Bubalo M, Vidovi? S, Radoj?i? Redovnikovi? I, Joki? S. Green solvents for green technologies. J Chem Technol Biotechnol. 2015;90(9):1631–1639.

Kerton FM, Marriott R. Alternative Solvents for Green Chemistry. 2nd ed. Cambridge: Royal Society of Chemistry; 2013.

Chemat F, Vian MA, Cravotto G. Green extraction of natural products: concept and principles. Int J Mol Sci. 2012;13(7):8615–8627.

Buszewski B, Szultka M. Past, present, and future of solid phase extraction: a review. Crit Rev Anal Chem. 2012;42(3):198–213.

Kataoka H. New trends in sample preparation for clinical and pharmaceutical analysis. TrAC Trends Anal Chem. 2003;22(4):232–244.

Majors RE. Ultra-high-pressure liquid chromatography: faster, better, greener. LC GC Eur. 2005;18:8–14.Lesellier E, West C. The many faces of packed column supercritical fluid chromatography—a critical review. J Chromatogr A. 2015;1382:2–46.

Wang J. Electrochemical detection for microscale analytical systems: a review. Talanta. 2002;56(2):223–231.

Lord H, Pawliszyn J. Evolution of solid-phase microextraction technology. J Chromatogr A. 2000;885(1–2):153–193.

Reyes DR, Iossifidis D, Auroux PA, Manz A. Micro total analysis systems. Anal Chem. 2002;74(12):2623–2636.

Murali Krishnam Raju P, Shyamala P, Venkata Narayana B, Dantuluri HSNR, Bhupatiraju RV. A fast, validated UPLC method coupled with PDA-QDa detectors for impurity profiling in betamethasone acetate and betamethasone phosphate injectable suspension and isolation, identification, characterization of two thermal impurities. Annales Pharmaceutiques Françaises. 2022 Nov;80(6):837–52.

Kaufmann B, Christen P. Recent extraction techniques for natural products: microwave-assisted extraction and pressurized solvent extraction. Phytochem Anal. 2002;13(2):105–113.

Keith LH, Gron LU, Young JL. Green analytical methodologies. Chem Rev. 2007;107(6):2695–2708.

Kralisch D, Ott D, Gericke D. Rules and benefits of life cycle assessment in green chemical process and synthesis design. Green Chem. 2015;17:123–145.

Mohan Kk, Patrudu Tb, Burle Gs, Salakolusu S, Raju Pvn, Jonnalagadda Sb, et al. Isolation and structural elucidation of an unknown novel impurity in sulfasalazine by high-performance liquid chromatography coupled to mass spectroscopy and toxicology prediction. Chinese Journal of Analytical Chemistry [Internet]. 2025 Jul 19;53(11):100601.

K.T.K. Reddy, G. Surendra, E.J. Mart, R.H. Babu, M.S. Arabath S.A., P. Erukulla, K.V. Kandimalla, P.V.N. Raju, Computational Identification of Natural Product–Based Aryl Hydrocarbon Receptor Modulators for Psoriasis Therapy. Chem. Methodol., 2026, 10(4) 450-464

P. Erukulla, P.V. Narasimha Raju, K.T. Kumar Reddy, V.R. Singamaneni, A. Pathak, S. Kumar Yadav, M. Sandeep Kumar,A.A. Mohathasim Billah. Emerging Analytical Techniques for Detection of Environmental Pollutants: A Review. Adv. J.Chem. A, 2026, 9(6), 962-996.

R. Hechhu, K. Krishnan, V. Singamaneni, P.V.N. Raju, P. Erukulla, K.V. Kandimalla, R.H. Babu, N. Vidiyala, GC-MS-Based Phytochemical Analysis, In-depth ADMET Screening and Molecular Docking Targeting EGFR for Anticancer Potential, Chem. Methodol., 2026, 10(5) 465-488

S.M. Bairagi, J.G. Wagh, A.R. Thanage, P. Venkata Narasimha Raju, P. Erukulla, K. Vamsi Kandimalla, A. Manukonda, R. Hari Babu. Green Extraction, Antioxidant, and Hepatoprotective Evaluation of Calotropis procera Leaf Extract. Asian Journal of Green Chemistry, 10 (3) 2026, 430-449.

Bonu P, B C, A HVS, M D, B A. RP-HPLC Method Development and Validation for the Simultaneous Determination of Candesartan cilexitil and Hydrochlorothiazide. Journal of Innovations in Applied Pharmaceutical Science (JIAPS). 2026 Apr 13;33–6.

M PE. advances in chromatographic and spectroscopic characterization of blue pea pigments and phenolics. Journal of Innovations in Applied Pharmaceutical Science (JIAPS). 2026 Feb 27;7–12.

Lapkin AA, Constable DJC. Green Chemistry Metrics: Measuring and Monitoring Sustainable Processes. Oxford: Wiley-Blackwell; 2008.