DEVELOPMENT AND VALIDATION OF STABILITY INDICATING RP-UHPLC METHOD FOR THE ESTIMATION OF IMEGLIMIN HYDROCHLORIDE USED FOR THE TREATMENT OF METABOLIC DISORDER DIABETES MELLITUS

AVNISH JAIN; LOVE KUMAR SONI; RAJESH SHARMA

doi:10.22159/ijap.2023v15i6.49757

Authors

AVNISH JAIN School of Pharmacy, Devi Ahilya Vishwavidyalaya, Ring Road, Indore, India
LOVE KUMAR SONI School of Pharmacy, Devi Ahilya Vishwavidyalaya, Ring Road, Indore, India
RAJESH SHARMA School of Pharmacy, Devi Ahilya Vishwavidyalaya, Ring Road, Indore, India

DOI:

https://doi.org/10.22159/ijap.2023v15i6.49757

Keywords:

Imeglimin hydrochloride, RP-UHPLC, Development, Validation, Stability indicating

Abstract

Objective: The present work was aimed to develop and validate a novel, simple, rapid, consistent, and sensitive stability indicating reverse phase ultra-high-performance liquid chromatographic (RP-UHPLC) method for the determination of oral anti-diabetic drug Imeglimin Hydrochloride in bulk and pharmaceuticals dosage form as per the technical recommendations of International Council for Harmonization guidelines for human use pharmaceutical (ICH-Q2(R1)).

Methods: A novel simple, selective, stable and sensitive stability indicating method which used isocratic RP-UHPLC methodology for the quantitative measurement of Imeglimin Hydrochloride was developed. The chromatographic separation of Imeglimin Hydrochloride was achieved on RP-UHPLC equipped with Hypersil gold ODS endcapped column of dimensions (150x4.6 mm, 3micron) using isocratic elution with a mobile phase consisting of water: acetonitrile in a ratio of (15:85% v/v) at a flow rate of 1 ml/min with an injection volume of 20 µl. All measurements are done on 240 nm using eight channels Dionex Ultimate 3000 PDA detector equipped with chromeleon data acquisition system for data integration. Validation of the proposed method was carried out according to the (ICH-Q2 (R1)) guidelines.

Results: The retention time of the Imeglimin Hydrochloride was found to be 3.831 with excellent absorbance sensitivity at 240 nm wavelength. The linear regression equation was found to be y = 3199x+1605.5 with a correlation coefficient (R²)>0.999 which shows excellent linear correlation. Specificity, linearity, precision, accuracy robustness, LOD and LOQ were determined for method validation and results were found to be well within recommended limits as per ICH guidelines.

Conclusion: The proposed stability indicating reverse phase ultra-high-performance liquid chromatographic (RP-UHPLC) method was found to be fast, affordable, robust, precise and specific for estimation of Imeglimin Hydrochloride in pharmaceutical dosage form.

Downloads

Download data is not yet available.

References

International Diabetic Federation for Type 2. Available from: http://www.idf.org/aboutdiabetes/type-2diabetes. [Last accessed on 31 Oct 2023]

Hallakou Bozec S, Vial G, Kergoat M, Fouqueray P, Bolze S, Borel AL. Mechanism of action of imeglimin: a novel therapeutic agent for type 2 diabetes. Diabetes Obes Metab. 2021;23(3):664-73. doi: 10.1111/dom.14277, PMID 33269554.

Hallakou Bozec S, Kergoat M, Moller DE, Bolze S. Imeglimin preserves islet β-cell mass in type 2 diabetic ZDF rats. Endocrinol Diabetes Metab. 2021;4(2):e00193. doi: 10.1002/edm2.193, PMID 33855202.

Olokoba AB, Obateru OA, Olokoba LB. Type 2 diabetes mellitus: a review of current trends. Oman Med J. 2012;27(4):269-73. doi: 10.5001/omj.2012.68, PMID 23071876.

Introduction to diabetes. Available from: https://www.healthline.com/health/diabetes.

Vuylsteke V, Chastain LM, Maggu GA, Brown C. Imeglimin: a potential new multi-target drug for type 2 diabetes. Drugs RD. 2015;15(3):227-32. doi: 10.1007/s40268-015-0099-3, PMID 26254210.

Doupis J, Baris N, Avramidis K. Imeglimin: a new promising and effective weapon in the treatment of type 2 diabetes. Touch Rev Endocrinol. 2021;17(2):88-91. doi: 10.17925/EE.2021.17.2.88, PMID 35118453.

Chen C, Cohrs CM, Stertmann J, Bozsak R, Speier S. Human beta cell mass and function in diabetes: recent advances in knowledge and technologies to understand disease pathogenesis. Mol Metab. 2017;6(9):943-57. doi: 10.1016/j.molmet.2017.06.019, PMID 28951820.

Yanai H, Adachi H, Hakoshima M, Katsuyama H. Glucose-lowering effects of imeglimin and its possible beneficial effects on diabetic complications. Biology (Basel). 2023;12(5):726. doi: 10.3390/biology12050726, PMID 37237539.

Detaille D, Vial G, Borel AL, Cottet Rouselle C, Hallakou Bozec S, Bolze S. Imeglimin prevents human endothelial cell death by inhibiting mitochondrial permeability transition without inhibiting mitochondrial respiration. Cell Death Discov. 2016;2:15072. doi: 10.1038/cddiscovery.2015.72, PMID 27551496.

Sanada J, Obata A, Fushimi Y, Kimura T, Shimoda M, Ikeda T. Imeglimin exerts favorable effects on pancreatic β-cells by improving morphology in mitochondria and increasing the number of insulin granules. Sci Rep. 2022;12(1):13220. doi: 10.1038/s41598-022-17657-3, PMID 35918386.

Vial G, Lamarche F, Cottet Rousselle C, Hallakou Bozec S, Borel AL, Fontaine E. The mechanism by which imegliminin hibits gluconeogenesis inrat liver cells. Endo-Crinol Diabetes Metab. 2021;4(2):e00211. doi: 10.1002/edm2.211.

Yingyue Q, Sugawara K, Takahashi H, Yokoi N, Ohbayashi K, Iwasaki Y. Stimulatory effect of imeglimin on incretin secretion. J Diabetes Investig. 2023;14(6):746-55. doi: 10.1111/jdi.14001, PMID 36977210.

Hallakou Bozec S, Kergoat M, Fouqueray P, Bolze S, Moller DE. Imeglimin amplifies glucose-stimulated insulin release from diabetic islets via a distinct mechanism of action. PLOS ONE. 2021;16(2):e0241651. doi: 10.1371/journal.pone.0241651, PMID 33606677.

Theurey P, Vial G, Fontaine E, Monternier PA, Fouqueray P, Bolze S. Reduced lactic acidosis risk with imeglimin: comparison with Metformin. Physiol Rep. 2022;10(5):e15151. doi: 10.14814/phy2.15151, PMID 35274817.

Hozumi K, Sugawara K, Ishihara T, Ishihara N, Ogawa W. Effects of imeglimin on mitochondrial function, AMPK activity, and gene expression in hepatocytes. Sci Rep. 2023;13(1):746. doi: 10.1038/s41598-023-27689-y, PMID 36639407.

Salvi AS, Khambkar MS, Dr Lahu D Hingane. Development and validation of RP-HPLC method for estimation of anti-diabetic drug in bulk and tablet dosage form. Journal of Emerging Tech Innovative Research. 2023;10:366-78.

ICH Guidelines Q2 (R1) Draft. Validation of analytical method. 2nd Revision; 2003.

ICH Guidelines Q1A (R2) Draft. Stability testing of new drug substance and products. 2nd Revision; 2003.

Bakshi M, Singh S. Development of validated stability-indicating assay methods-critical review. J Pharm Biomed Anal. 2002;28(6):1011-40. doi: 10.1016/s0731-7085(02)00047-x, PMID 12049968.

Smela MJ. Regulatory considerations for stability-indicating analytical methods in drug substance and drug product testing. Am Pharm Rev. 2005;8(3):51-4.

FDA guidance for industry. Anal Proc Methods Validation (Draft Guid); 2000.