Objective: To study the stability and hydrolysis kinetics of genotoxic impurities methanesulfonates at trace levels, including methyl methanesulfonate（MMS）, ethyl methanesulfonate（EMS）, propyl methanesulfonate （PMS）and isopropyl methanesulfonate（IMS）. Methods: Solutions of methansulfonates were prepared in acetonitrile/water（80∶20, v/v）and placed under 298 K, 313 K and 323 K, respectively. The methanesulfonates solutions were transformed into corresponding alkyl iodides for headspace GC/MS detection by utilizing the sodium iodide solution as the derivative reagent. The concentrations of the methansulfonates were monitored periodically by their corresponding derivative products of alkyl iodides. Results: EMS and PMS were stable under the above mentioned temperatures, while MMS and IMS were found to be stable only under 298 K. As the temperature raised to 313 K and 323 K, both MMS and IMS degraded due to the hydrolysis reaction on their corresponding ester groups. Both the hydrolysis kinetic parameters were obtained. Conclusion: Different kinds of methanesulfonates possess characteristic stability properties, whereas, indicating that serious attentions should be paid on the strict requirements of the temperature control for preparing the sample solutions during assay determinations.
CHENG Bi-yun, CHEN Huan-huan, HAN Hai-yun, SUN Ling, XU Bin, CHEN Dong-ying,
. Study on the stability and hydrolysis kinetics of genotoxic impurities methanesulfonates*[J]. Chinese Journal of Pharmaceutical Analysis, 2021
, 41(3)
: 460
-465
.
DOI: 10.16155/j.0254-1793.2021.03.11
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