A sensitive direct chiral liquid chromatography tandem mass spectrometry method for the enantio—Selective analysis of imeglimin in formulation

Sangamithra Ramalingam Meyyanathan Nainar Subramania Babu Basuvan Ramesh Jaganathan Anandha Jothi Dhavamani Nagesh Kumar Kandukuri Ratnam Venkata Parimi Sandeep Bodduna   

Open Access   

Published:  Apr 05, 2023

DOI: 10.7324/JAPS.2023.132349

The purpose of this study was to separate and develop a sensitive chiral liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique to estimate the (+) and (−) enantiomers of imeglimin in its formulation and validate individual enantiomer of the drug. Imeglimin is used to treat type-2 diabetes (T2D). The chiral stationary phase was reverse phase Chiralpak IG-3 (100 × 4.6 mm, 3 μm), whereas the isocratic mobile phase was methanol and 10 mM ammonium acetate (95:5 v/v ratio) and the flow rate was 0.5 ml/minutes. The resolution of the (+) and (−) enantiomers was monitored using LC-ESI-MS/MS in positive transition at 155.0 m/z (M+H) for imeglimin. The (+) and (−) linearity ranges from 10 to 100 ng/ml. The correlation coefficient (R2) of the (+) and (−) imeglimin enantiomers was found to be linear. The retention time of the (+) and (−) enantiomers of the drug was 2.876 and 4.325 minutes and the total run time of the chromatographic resolution was 5 minutes. As a result, our goal is to separate the enantiomers and develop a fast, sensitive, and cost-effective method for estimating (+) and (−) enantiomers in its formulation.

Keyword:     Imeglimin (+) and (-) enantiomers LC-ESI-MS/MS validation and formulation


Ramalingam S, Subramania MN, Basuvan B, Jaganathan R, Dhavamani AJ, Kandukuri NK, Parimi RV, Bodduna S. A sensitive direct chiral liquid chromatography-tandem mass spectrometry method for the enantio—Selective analysis of imeglimin in formulation. J Appl Pharm Sci, 2023. https://doi.org/10.7324/JAPS.2023.132349

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

HTML Full Text


Ates H, Younes AA, Mangelings D, Vander Heyden Y. Enantioselectivity of polysaccharide-based chiral selectors in polar organic solvents chromatography: implementation of chlorinated selectors in a separation strategy. J Pharm Biomed Anal, 2013; 74:1-3. https://doi.org/10.1016/j.jpba.2012.09.025

Bhowmick D, Sang Y, Santra K, Halbauer M, Capua E, Paltiel Y, Naaman R, Tassinari F. Simultaneous high-purity enantiomeric resolution of conglomerates using magnetic substrates. Cryst Growth Des, 2021; 21(5):2925-31. https://doi.org/10.1021/acs.cgd.1c00093

Doupis J, Baris N, Avramidis K. Imeglimin: a new promising and effective weapon in the treatment of type 2 diabetes. TouchREV Endocrinol, 2021; 17(2):88. https://doi.org/10.17925/EE.2021.17.2.88

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

ICH. Q3B validation of analytical procedures: methodology. International Conference on Harmonization, November 1996. [ONLINE] Available via https://www.fda.gov/downloads/drugs/guidances/ ucm073384. pdf (Accessed 20 August 2019).

Liu Y, Tian A, Wang X, Qi J, Wang F, Ma Y, Ito Y, Wei Y. Fabrication of chiral amino acid ionic liquid modified magnetic multifunctional nanospheres for centrifugal chiral chromatography separation of racemates. J Chromatogr A, 2015; 26(1400):40-6. https://doi.org/10.1016/j.chroma.2015.04.045

Mukherjee AS, Bera AJ. Importance of chirality and chiral chromatography in pharmaceutical industry: a detailed study. J Chem Pharm Sci, 2012; 2(4):334-46.

Song L, Pan M, Zhao R, Deng J, Wu Y. Recent advances, challenges and perspectives in enantioselective release. J Control Release, 2020; 10(324):156-71. https://doi.org/10.1016/j.jconrel.2020.05.019

Tang L, Swezey RR, Green CE, Lee MS, Bunin DI, Parman T. A tandem liquid chromatography and tandem mass spectrometry (LC/LC- MS/MS) technique to separate and quantify steroid isomers 11β-methyl-19- nortestosterone and testosterone. J Chromatogr B, 2022; 15(1193):123165. https://doi.org/10.1016/j.jchromb.2022.123165

Tomita Y, Hansson E, Mazuir F, Wellhagen GJ, Ooi QX, Mezzalana E, Kitamura A, Nemoto D, Bolze S. Imeglimin population pharmacokinetics and dose adjustment predictions for renal impairment in Japanese and Western patients with type 2 diabetes. Clin Transl Sci, 2022; 15(4):1014-26. https://doi.org/10.1111/cts.13221

Wacharine-Antar S, Levilain G, Dupray V, Coquerel G. Resolution of (±)-imeglimin-2, 4-dichlorophenylacetate methanol solvate by preferential crystallization. Org Process Res Dev, 2010; 14(6):1358-63. https://doi.org/10.1021/op100173r

Article Metrics

0 Absract views 2 PDF Downloads 2 Total views

   Abstract      Pdf Download

Related Search

By author names

Citiaion Alert By Google Scholar

Name Required
Email Required Invalid Email Address

Comment required
Similar Articles