Abstract
AbstractAlalevonadifloxacin mesylate (ALA), pro-drug of levonadifloxacin is a new antibiotic approved in India to treat infections caused by Gram-positive bacteria. Alkyl mesylates (AMs) are known genotoxic impurities (GTI’s) formed in drug substances isolated as mesylate salts. Time-dependent selected reaction monitoring (t-SRM)-based gas chromatography tandem mass spectrometry (GC-MS/MS) method has been developed for trace estimation of AMs, namely, methyl methane sulfonate (MMS), ethyl methane sulfonate (EMS) and isopropyl methane sulfonate (IMS) in ALA. Liquid-liquid extraction (LLE) procedure using dichloromethane (DCM) as an extracting solvent was employed to extract AMs from the drug substance. Automatic selective reaction monitoring (auto-SRM) tool was applied to identify the most intense SRM pair of the ions to achieve the highest sensitivity. The method was validated in terms of specificity, linearity, sensitivity, precision, and accuracy. The limit of quantitation (LOQ) for the MMS, EMS and IMS were 5, 10, and 20 ng/g of ALA, respectively. For all analytes, the correlation coefficient (R) were greater than 0.9975 in the concentration range of 3.0–260 ng/mL. Mean recovery of all analytes was in the range of 91.77 to 97.65%.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Environmental Science,General Biochemistry, Genetics and Molecular Biology,General Materials Science,General Chemistry
Reference30 articles.
1. Alzaga R, Ryan RW, Taylor-Worth K, Lipczynski AM, Szucs R, Sandra P. Generic approach for the determination of residues of alkylating agents in active pharmaceutical ingredients by in situ derivatization–headspace-gas chromatography-mass spectrometry. J Pharm Biomed Anal. 2007;45:472–9. https://doi.org/10.1016/j.jpba.2007.07.017.
2. An J, Sun M, Bai L, Chen T, Liu DQ, Kord A. A practical derivatization LC/MS approach for determination of trace level alkyl sulfonates and dialkyl sulfates genotoxic impurities in drug substances. J Pharm Biomed Anal. 2008;48:1006–10. https://doi.org/10.1016/j.jpba.2008.06.019.
3. Andrew T, Delaney JEJ, Stephen CE, Karine J, Karen TW, Andrew L, Wilfried H, Van R, David PE, Kevin LF, Simon G, Rolf SO, Pat S, Frank D. A detailed study of sulfonate ester formation and solvolysis reaction rates and application toward establishing sulfonate ester control in pharmaceutical manufacturing processes. Org Process Res Dev. 2010;14:999–1007. https://doi.org/10.1021/op900301n.
4. Chugh R, Lakdavala F, Bhatia A. Safety and pharmacokinetics of multiple ascending doses of WCK 771 and WCK 2349, Abstract: P1268. Amsterdam: 26th Eur Congr Clin Microbiol Infect Dis; 2016.
5. Chugh R, Lakdavla F, Bhagwat S, Patel LM, Bhatia A. Food effect and absolute bioavailability study of WCK 2349 and WCK 771 in healthy adult human volunteers in U.S., Abstract: A-039, 55th Intersci Conf Antimicrob Agents Chemother., San Diego, CA. Washington, DC: American Society for Microbiology; 2015.
Cited by
5 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献