Time-dependent selected reaction monitoring-based GC-MS/MS method for estimation of genotoxic impurities in new antibacterial agent: alalevonadifloxacin mesylate
Abstract Alalevonadifloxacin 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 sele...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SpringerOpen
2020-06-01
|
| Series: | Journal of Analytical Science and Technology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40543-020-00214-w |
| _version_ | 1818135049645588480 |
|---|---|
| author | Vinod K. Ahirrao Rajiv A. Jadhav Vipul P. Rane Harshal R. Bhamare Ravindra D. Yeole |
| author_facet | Vinod K. Ahirrao Rajiv A. Jadhav Vipul P. Rane Harshal R. Bhamare Ravindra D. Yeole |
| author_sort | Vinod K. Ahirrao |
| collection | DOAJ |
| description | Abstract Alalevonadifloxacin 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%. |
| first_indexed | 2024-12-11T09:18:20Z |
| format | Article |
| id | doaj.art-3eb5d9728342463e962ab0b796486c24 |
| institution | Directory Open Access Journal |
| issn | 2093-3371 |
| language | English |
| last_indexed | 2024-12-11T09:18:20Z |
| publishDate | 2020-06-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Journal of Analytical Science and Technology |
| spelling | doaj.art-3eb5d9728342463e962ab0b796486c242022-12-22T01:13:18ZengSpringerOpenJournal of Analytical Science and Technology2093-33712020-06-011111910.1186/s40543-020-00214-wTime-dependent selected reaction monitoring-based GC-MS/MS method for estimation of genotoxic impurities in new antibacterial agent: alalevonadifloxacin mesylateVinod K. Ahirrao0Rajiv A. Jadhav1Vipul P. Rane2Harshal R. Bhamare3Ravindra D. Yeole4Wockhardt Research CentreWockhardt Research CentreWockhardt Research CentreWockhardt Research CentreWockhardt Research CentreAbstract Alalevonadifloxacin 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%.http://link.springer.com/article/10.1186/s40543-020-00214-wAlalevonadifloxacinGC-MS/MSTime-dependent SRMAlkyl mesylates |
| spellingShingle | Vinod K. Ahirrao Rajiv A. Jadhav Vipul P. Rane Harshal R. Bhamare Ravindra D. Yeole Time-dependent selected reaction monitoring-based GC-MS/MS method for estimation of genotoxic impurities in new antibacterial agent: alalevonadifloxacin mesylate Journal of Analytical Science and Technology Alalevonadifloxacin GC-MS/MS Time-dependent SRM Alkyl mesylates |
| title | Time-dependent selected reaction monitoring-based GC-MS/MS method for estimation of genotoxic impurities in new antibacterial agent: alalevonadifloxacin mesylate |
| title_full | Time-dependent selected reaction monitoring-based GC-MS/MS method for estimation of genotoxic impurities in new antibacterial agent: alalevonadifloxacin mesylate |
| title_fullStr | Time-dependent selected reaction monitoring-based GC-MS/MS method for estimation of genotoxic impurities in new antibacterial agent: alalevonadifloxacin mesylate |
| title_full_unstemmed | Time-dependent selected reaction monitoring-based GC-MS/MS method for estimation of genotoxic impurities in new antibacterial agent: alalevonadifloxacin mesylate |
| title_short | Time-dependent selected reaction monitoring-based GC-MS/MS method for estimation of genotoxic impurities in new antibacterial agent: alalevonadifloxacin mesylate |
| title_sort | time dependent selected reaction monitoring based gc ms ms method for estimation of genotoxic impurities in new antibacterial agent alalevonadifloxacin mesylate |
| topic | Alalevonadifloxacin GC-MS/MS Time-dependent SRM Alkyl mesylates |
| url | http://link.springer.com/article/10.1186/s40543-020-00214-w |
| work_keys_str_mv | AT vinodkahirrao timedependentselectedreactionmonitoringbasedgcmsmsmethodforestimationofgenotoxicimpuritiesinnewantibacterialagentalalevonadifloxacinmesylate AT rajivajadhav timedependentselectedreactionmonitoringbasedgcmsmsmethodforestimationofgenotoxicimpuritiesinnewantibacterialagentalalevonadifloxacinmesylate AT vipulprane timedependentselectedreactionmonitoringbasedgcmsmsmethodforestimationofgenotoxicimpuritiesinnewantibacterialagentalalevonadifloxacinmesylate AT harshalrbhamare timedependentselectedreactionmonitoringbasedgcmsmsmethodforestimationofgenotoxicimpuritiesinnewantibacterialagentalalevonadifloxacinmesylate AT ravindradyeole timedependentselectedreactionmonitoringbasedgcmsmsmethodforestimationofgenotoxicimpuritiesinnewantibacterialagentalalevonadifloxacinmesylate |