Bioanalytical Method Validation of Metformin Hydrochloride in Human Plasma by HPLC-UV for Preliminary Population-Based Pharmacokinetic Modeling Study

https://doi.org/10.22146/ijc.77903

Dimas Adhi Pradana(1*), Erna Kristin(2), Akhmad Kharis Nugroho(3), Dwi Aris Agung Nugrahaningsih(4), Mustofa Mustofa(5), Ari Wibowo(6)

(1) Department of Pharmacy, Universitas Islam Indonesia, Jl. Kaliurang km. 14, Yogyakarta 55584, Indonesia; Department of Pharmacology and Therapy, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Jl. Farmako, Sekip Utara, Yogyakarta 55281, Indonesia
(2) Department of Pharmacology and Therapy, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Jl. Farmako, Sekip Utara, Yogyakarta 55281, Indonesia
(3) Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia
(4) Department of Pharmacology and Therapy, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Jl. Farmako, Sekip Utara, Yogyakarta 55281, Indonesia
(5) Department of Pharmacology and Therapy, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Jl. Farmako, Sekip Utara, Yogyakarta 55281, Indonesia
(6) Department of Pharmacy, Universitas Islam Indonesia, Jl. Kaliurang km. 14, Yogyakarta 55584, Indonesia
(*) Corresponding Author

Abstract


This study aims to validate the method for measuring metformin hydrochloride plasma concentrations using High-Performance Liquid Chromatography (HPLC). This research performed chromatography on a 250 mm 4.6 mm 5 µm purosphere® Star RP-18 column at ambient temperature with a UV detector system at 233 nm. The mobile phase components were 70% phosphate buffer (KH2PO4) (10 mM), sodium dodecyl sulfate (0.3 mM), and 30% acetonitrile. It was pumped at an isocratic flow rate of 1.2 mL/min. Metformin HCl and ranitidine HCl (internal standard) were extracted using acetonitrile. The calibration curve was linear (R2 = 0.9998) in the 0.18–6 µg/mL concentration range. The lower limit of quantification (LLOQ) was 0.18 µg/mL. For intraday accuracy and precision, the percent difference and the coefficient of variation were less than 4 and 7%, and for inter-day were lower than 8 and 6%. The recovery average was 100.96%. The short-term plasma stability test was stable at 24 h at ambient temperature, and the long-term stability test was steady for 30 d at −20 °C. It was also stable after three freeze-thaw cycles. The method meets selectivity, sensitivity, linearity, accuracy, precision, recovery, carryover, and stability requirements and can be applied to population-based pharmacokinetic modeling.


Keywords


human plasma; HPLC-UV; metformin HCl; pharmacokinetic; validation

Full Text:

Full Text PDF


References

[1] Shurrab, N.T., and Arafa, E.S.A., 2020, Metformin: A review of its therapeutic efficacy and adverse effects, Obes. Med., 17, 100186.

[2] Sanchez-Rangel, E., and Inzucchi, S.E., 2017, Metformin: Clinical use in type 2 diabetes, Diabetologia, 60 (9), 1586–1593.

[3] Hostalek, U., Gwilt, M., and Hildemann, S., 2015, Therapeutic use of metformin in prediabetes and diabetes prevention, Drugs, 75 (10), 1071–1094.

[4] Flory, J., and Lipska, K., 2019, Metfonim in 2019, JAMA, 321 (19), 1926–1927.

[5] Indonesian Association of Endocrinologists (Perkeni), 2019, Consensus on Type-2 Diabetes Mellitus Control and Prevention, Jakarta, Indonesia.

[6] Johnson, N.P., 2014, Metformin use in women with polycystic ovary syndrome, Ann. Transl. Med., 2 (6), 56.

[7] Podhorecka, M., Ibanez, B., and Dmoszyńska, A., 2017, Metformin - Its potential anti-cancer and anti-aging effects, Postepy Hig. Med. Dosw., 71, 170–175.

[8] Center for Drug Evaluation and Research, 2013, Chemistry review(s): ActoPlus MET™ XR (pioglitazone HCl/metformin HCl extended release) Tablets, Application Number 22-024, Lincolnshire, UK.

[9] Kaur, G., Garg, S., Sharma, P., and Sud, D., 2021, A review on high-performance liquid chromatographic methods for the determination of metformin, Curr. Anal. Chem., 17 (6), 754–767.

[10] Fachi, M.M., Leonart, L.P., Cerqueira, L.B., Pontes, F.L.D., de Campos, M.L., and Pontarolo, R., 2017, A systematic and critical review on bioanalytical method validation using the example of simultaneous quantitation of antidiabetic agents in blood, J. Chromatogr. B, 1055-1056, 61–71.

[11] Mohamed, D., Elshahed, M.S., Nasr, T., Aboutaleb, N., and Zakaria, O., 2019, Novel LC-MS/MS method for analysis of metformin and canagliflozin in human plasma: Application to a pharmacokinetic study, BMC Chem., 13 (1), 82.

[12] Amini, H., Ahmadiani, A., and Gazerani, P., 2005, Determination of metformin in human plasma by high-performance liquid chromatography, J. Chromatogr. B, 824 (1-2), 319–322.

[13] Gabr, R.Q., Padwal, R.S., and Brocks, D.R., 2010, Determination of metformin in human plasma and urine by high-performance liquid chromatography using small sample volume and conventional octadecyl silane column, J. Pharm. Pharm. Sci., 13 (4), 486–494.

[14] Nielsen, F., Christensen, M.M.H., and Brøsen, K., 2014, Quantitation of metformin in human plasma and urine by hydrophilic interaction liquid chromatography and application to a pharmacokinetic study, Ther. Drug Monit., 36 (2), 211–217.

[15] Abdessadek, M., Tadmori, A.E., El-Attari, A., Diarra, M., Magoul, R., Ajdi, F., El-Ouezzani, S., and Khabbal, Y., 2015, Simple HPLC-UV method for determination of metformin in human plasma and erythrocytes application to therapeutic drug monitoring, Int. J. Pharm. Pharm. Sci., 7 (11), 35–39.

[16] Nikam, N., Maru, A., Jadhav, A., and Malpure, P., 2019, Analytical method development and validation of metformin hydrochloride by using RP-HPLC with ICH guidelines, Int. J. Trend Sci. Res. Dev., 3 (3), 415–419.

[17] Gedawy, A., Al-Salami, H., and Dass, C.R., 2019, Development and validation of a new analytical HPLC method for simultaneous determination of the antidiabetic drugs, metformin and gliclazide, J. Food Drug Anal., 27 (1), 315–322.

[18] Chhetri, H.P., Thapa, P., and Van Schepdael, A., 2014, Simple HPLC-UV method for the quantification of metformin in human plasma with one step protein precipitation, Saudi Pharm. J., 22 (5), 483–487.

[19] Ningrum, V.D.A., Wibowo, A., Fuaida, I., Ikawati, Z., Sadewa, A.H., and Ikhsan, M.R., 2018, Validation of an HPLC-UV method for the determination of metformin hydrochloride in spiked-human plasma for the application of therapeutic drug monitoring, Res. J. Pharm. Technol., 11 (6), 2197–2202.

[20] Li, L., Guan, Z., Li, R., Zhao, W., Hao, G., Yan, Y., Xu, Y., Liao, L., Wang, H., Gao, L., Wu, K., Gao, Y., Li, Y., 2020, Population pharmacokinetics and dosing optimization of metformin in Chinese patients with type 2 diabetes mellitus, Medicine, 99 (46), e23212

[21] Kajbaf, F., De Broe, M.E., and Lalau, J.D., 2016, Therapeutic concentrations of metformin: A systematic review, Clin. Pharmacokinet., 55 (4), 439–59.

[22] U.S. Department of Health and Human Services Food and Drug Administration, Center for Drug Evaluation and Research (CDER), and Center for Veterinary Medicine (CVM), 2018, Bioanalytical Method Validation: Guidance for Industry, Silver Spring, Maryland, USA.

[23] Committee for Medicinal Products for Human Use, 2022, ICH Guideline M10 on Bioanalytical Method Validation, European Medicines Agency, Amsterdam, Netherlands.

[24] U.S. Department of Health and Human Services Food and Drug Administration, Center for Drug Evaluation and Research (CDER), and Center for Veterinary Medicine (CVM), 2022, Population Pharmacokinetics: Guidance for Industry, Silver Spring, Maryland, USA.

[25] Traynard, P., Ayral, G., Twarogowska, M., and Chauvin, J., 2020, Efficient pharmacokinetic modeling workflow with the MonolixSuite: A case study of remifentanil, CPT: Pharmacometrics Syst. Pharmacol., 9 (4), 198–210.

[26] Harahap, Y., Dianpratami, K., Wulandari, M., and Rahmawati, R., 2012, Validation of metformin hydrochloride in human plasma by HPLC-photo diode array (PDA) for application of bioequivalence Study, J. Life Sci., 6, 20–27.

[27] Niraula, T.P., Bhattarai, A., and Chatterjee, S.K., 2014, Sodium dodecyl sulphate: A very useful surfactant for scientific investigations, J. Knowl. Innovation, 2 (1), 111–113.

[28] Patyra, E., and Kwiatek, K., 2021, Application of micellar mobile phase for quantification of sulfonamides in medicated feeds by HPLC-DAD, Molecules, 26 (13) 3791.

[29] Rudakov, O.B., Rudakova, L.V., and Selemenev, V.F., 2018, Acetonitrile as tops solvent for liquid chromatography and extraction, J. Anal. Chromatogr. Spectrosc., 1, 883.

[30] Center for Drug Evaluation and Research (CDER), 1994, Reviewer Guidance: Validation of Chromatographic Methods, Rockville, Maryland, USA.

[31] International Council for Harmonisation, 2022, ICH Guideline Q2(R2) on Validation of Analytical Procedures, European Medicines Agency, Amsterdam, Netherlands.



DOI: https://doi.org/10.22146/ijc.77903

Article Metrics

Abstract views : 2056 | views : 1640


Copyright (c) 2023 Indonesian Journal of Chemistry

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

 


Indonesian Journal of Chemistry (ISSN 1411-9420 /e-ISSN 2460-1578) - Chemistry Department, Universitas Gadjah Mada, Indonesia.

Web
Analytics View The Statistics of Indones. J. Chem.