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Multipurpose RP-HPLC Method for Simultaneous Estimation of Fixed-Dose Combinations of Anti-diabetic Drugs: Integrating Green, Economical, and Robust Approaches with Design of Experiments and White Analytical Chemistry

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Abstract

Background

Metformin hydrochloride is a common anti-diabetic medication, frequently prescribed in fixed-dose combinations for diabetes treatment. Various analytical methods, such as RP-HPLC and HPTLC, are employed to ensure the quality of these fixed-dose combinations. However, many of these methods utilized harmful organic solvents with potential environmental consequences. Consequently, there is a growing demand for greener and safer chromatographic methods. A recent concept of white analytical chemistry, emphasizes the development and assessment of chromatographic techniques based on validation, cost, time, and environmental sustainability.

Objectives

In line with this concept, an RP-HPLC method has been developed for the synchronous estimation of multiple fixed-dose combinations (FDCs) of metformin hydrochloride, utilizing low-toxic and economical solvents under a single chromatographic condition.

Methods

The RP-HPLC method was developed using the AQbD approach, which integrates analytical quality risk assessment and DoE principles. The goal was to reduce organic waste and ensure compliance with regulatory standards. The method was subsequently rigorously validated following ICH Q2 (R1) guidelines.

Results

The chromatographic separation of metformin and other drugs have been carried out using a Shim-Pack C18 column (250 mm × 4.6 mm, 5.0 µm) as stationary phase and the mobile phase, composed of ethanol: water (70 + 30, v/v) at pH 3.0 (adjusted using glacial acetic acid). The developed method was found to be specific, accurate, precise, robust and sensitive for estimation of multiple FDCs of metformin. The method was applied effectively to various metformin hydrochloride fixed-dose combinations, confirming label claim compliance. This method was also compared with published RP-HPLC methods, which were evaluated based on white analytical chemistry principles.

Conclusion

In conclusion, the proposed white analytical chemistry-driven RP-HPLC method offers a safe, cost-effective, and eco-friendly alternative to existing techniques for quality control and routine analysis of multiple fixed-dose combinations of metformin hydrochloride in the pharmaceutical industry.

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Availability of Data and Material

The data will be availed by corresponding author of manuscript on reasonable request.

Abbreviations

ICH:

International council for harmonization

RP-HPLC:

Reversed-phase high-pressure liquid chromatography

IP:

Indian Pharmacopoeia

PDE:

Permitted daily exposure

WAC:

White analytical chemistry

AQbD:

Analytical quality by design

AQRM:

Analytical quality risk management

DoE:

Design of experiments

CPPs:

Critical procedure parameters

CMPAs:

Critical method performance attributes

GAC:

Green analytical chemistry

QRM:

Quality risk management

MET:

Metformin hydrochloride

NATE:

Nateglinide

DGZ:

Dapagliflozin

GLB:

Glyburide

REPA:

Repaglinide

RSM:

Response surface modeling

AGREE:

Analytical greenness

GAPI:

Green analytical procedure index

NEMI:

National environmental method index

FDCs:

Fixed-dose combinations

APIs:

Active pharmaceutical ingredients

References

  1. Nowak MP, Weitecha-Posluszny R, Pawliszyn J (2021) White analytical chemistry: an approach to reconcile the principles of green analytical chemistry and functionality. Trends Anal Chem 138:116223. https://doi.org/10.1016/j.trac.2021.116223

    Article  CAS  Google Scholar 

  2. (2016) International Council for Harmonization Q3C (R6) guideline, impurities: a guideline for residual solvent. pp 1–40

  3. Indian Pharmacopoeia 2018, Volume I, residual solvents, the Indian Pharmacopeia Commission, pp 987

  4. Byrne FP, Jin S, Paggiola G, Petchey THM, Clark JH, Farmer TJ, Hunt AJ, McElroy CR, Sherwood J (2016) Tools and techniques for solvent selection: green solvent selection guides. Sustain Chem Process 4(7):1–24. https://doi.org/10.1186/s40508-016-0051-z

    Article  CAS  Google Scholar 

  5. Stojanovic J, Krmar J, Otasevic B, Protic A (2023) Resource management in HPLC: Unveiling a green face of pharmaceutical analysis. Arhiv Za Farmaciju 73(2):146–171. https://doi.org/10.5937/arhfarm73-43479

    Article  Google Scholar 

  6. Kannaiah KP, Chanduluru HK, Obaydo RH, Lotfy HM, Erk N, Krishnan M, El Hamd MA (2023) Application of advanced environmentally benign assessment tools in determining ternary cardiovascular drug combination by RP-HPLC with analytical quality by design: application to stability indicating method evaluation. Sustain Chem Pharm 35:101197

    Article  CAS  Google Scholar 

  7. Patel A, Shah SA (2021) DoE-based analytical quality risk management for enhanced AQbD approach to economical and eco-friendly RP-HPLC method for synchronous estimation of multiple FDC products of antihypertensive drugs. J Chromatogr Sci 60(8):786–799. https://doi.org/10.1093/chromsci/bmab123

    Article  CAS  Google Scholar 

  8. Mistry KY, Shah SA (2022) DoE-based analytical failure modes critical effect analysis (AFMCEA) to a multipurpose-RP-HPLC method for the estimation of multiple FDC products of metformin hydrochloride using an analytical quality by design approach. J AOAC Int 105(4):986–998. https://doi.org/10.1093/jaoacint/qsac025

    Article  PubMed  Google Scholar 

  9. Patel AS, Shah SA (2023) Simultaneous estimation of telmisartan, chlorthalidone, amlodipine besylate and atorvastatin by RP-HPLC method for synchronous assay of multiple FDC products using analytical FMCEA-based AQbD approach. J Chromatogr Sci 61(2):160–171. https://doi.org/10.1093/chromsci/bmac030

    Article  CAS  PubMed  Google Scholar 

  10. Shahi A, Acharya A, Shah SA (2023) Chemometric and design of experiments based analytical quality by design and green chemistry approaches to the multipurpose high-pressure liquid chromatographic method for synchronous estimation of multiple fixed-dose combinations of azilsartan medoxomil. J AOAC Int 106(1):250–260. https://doi.org/10.1093/jaoacint/qsac086

    Article  Google Scholar 

  11. Prajapati B, Pulusu V, Shah S (2023) Multivariate analysis and response surface modeling to green analytical chemistry-based RP-HPLC-PDA method for chromatographic analysis of vildagliptin and remogliflozin etabonate. J AOAC Int 106(03):601–612. https://doi.org/10.1093/jaoacint/qsad013

    Article  PubMed  Google Scholar 

  12. Jariwala H, Prajapati B, Salunkhe M, Pulusu V, Shah S (2023) Application of principal component analysis and DoE driven green analytical chemistry concept to liquid chromatographic method for estimation of co-formulated anti-hypertensive drugs. J AOAC Int. https://doi.org/10.1093/jaoacint/qsad016

    Article  PubMed  Google Scholar 

  13. Patel A, Shah SA (2022) DoE-based analytical-FMCEA for enhanced AQbD approach to MEER-RP-HPLC method for synchronous estimation of fifteen antihypertensive pharmaceutical dosage forms. J AOAC Int 105(1):34–45. https://doi.org/10.1093/jaoacint/qsab097

    Article  PubMed  Google Scholar 

  14. Drug data bank of metformin hydrochloride/dapagliflozin/nateglinide/glyburide/ repaglinide, https://go.drugbank.com/salts/DBSALT000114/DB06292/DB00731, DB01016/DB00912. Accessed 22 May 2023

  15. Urooj A, Sundar PS, Vasanthi R, Raja MA, Dutt KR, Rao KNV, Ramana H (2017) Development and validation of RP-HPLC method for simultaneous estimation of dapagliflozin and metformin in bulk and synthetic mixture. World J Pharm Pharm Sci 6(7):2139–2150

    CAS  Google Scholar 

  16. Edla S, Sundhar BS (2014) New analytical method development and validation for the simultaneous estimation of metformin and glibenclamide in bulk and tablet dosage form using RP-HPLC. Rasayan J Chem 7(1):55–63

    CAS  Google Scholar 

  17. De AK, Dey AK, Biswas A (2012) Simultaneous estimation of metformin hydrochloride and glibenclamide by RP-HPLC method from combined tablet dosage form. Int J Sci Invent Today 1(2):98–105

    Google Scholar 

  18. Chengalva P, Parameswari A, Gingawar A (2016) Development and validation of RP-HPLC method for metformin hydrochloride and nateglinide in bulk and combined dosage forms. Int J Pharm Pharm Sci 8(4):267–271

    CAS  Google Scholar 

  19. Soni LK, Narsinghani T, Jain M (2012) Development and validation of RP-HPLC method for simultaneous estimation of metformin hydrochloride and repaglinide in the tablet dosage form. J Liq Chromatogr Relat Technol 35(3):385–392

    Article  CAS  Google Scholar 

  20. Jain M, Sharma A, Soni LK, Kabra M (2013) Method development and simultaneous estimation of metformin hydrochloride and repaglinide in the tablet dosage form. Asian J Pharm Res Dev 1(3):108–114

    Google Scholar 

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Acknowledgements

The Maliba Pharmacy College’s Principal and the Uka Tarsadia University’s Provost are thanked by the authors for their enormous help in providing the necessary infrastructure and instrumentation equipment to carry out the research endeavor. Their contributions were crucial to the accomplishment of this investigation.

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Authors and Affiliations

  1. Department of Quality Assurance, Maliba Pharmacy College, Maliba Campus, Bardoli-Mahuva Road, Tarsadi, Mahuva, Surat, Gujarat, 394 350, India

    Pintu Prajapati, Bageshree Rana & Ashish Mishra

  2. Department of Chemistry and Biochemistry, Ohio University, Anthens, OH, 45701, USA

    Veera Shakar Pulusu

Authors
  1. Pintu Prajapati
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  2. Bageshree Rana
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  3. Veera Shakar Pulusu
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  4. Ashish Mishra
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Contributions

Dr PP—drafting, conceptualization, supervision, review. BR—methodology and writing. VSP—review, software analysis handling and drafting. AM—supervision and review support.

Corresponding author

Correspondence to Pintu Prajapati.

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The authors of the manuscript already declared that they do not have any conflicts of interest for the publication of the manuscript.

Ethics Approval and Consent to Participate

Our research work does not include use of animal and human being. The manuscript has been solely submitted for publication in the future journal of pharmaceutical sciences. The authors of manuscript have declared that they do not have any conflicts of interest.

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Our research work does not include any human study. The manuscript entitles ‘Innovative RP-HPLC Method for Simultaneous Estimation of Fixed-Dose Combinations of Anti-diabetic Drugs: Integrating Green, Economical, and Robust Approaches with Design of Experiments and White Analytical Chemistry’ has been solely submitted to Future Journal of Pharmaceutical Sciences.

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Prajapati, P., Rana, B., Pulusu, V.S. et al. Multipurpose RP-HPLC Method for Simultaneous Estimation of Fixed-Dose Combinations of Anti-diabetic Drugs: Integrating Green, Economical, and Robust Approaches with Design of Experiments and White Analytical Chemistry. Chemistry Africa 7, 1385–1400 (2024). https://doi.org/10.1007/s42250-023-00835-9

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