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- Title
Simultaneous quantitation of two diastereoisomers of lobaplatin in rat plasma by supercritical fluid chromatography with tandem mass spectrometry and its application to a pharmacokinetic study.
- Authors
Meng, Xiangjun; Yang, Bo; Gao, Jingyi; Peng, Wenwen; Wang, Hao; Shi, Meiyun; Mortishire‐Smith, Russell; Yang, Yan; Gu, Jingkai
- Abstract
Lobaplatin, consisting of two diastereoisomers, is a third-generation platinum antineoplastic agent that has shown encouraging anticancer activity in a variety of tumor types. To investigate any stereospecificity in the pharmacokinetics of lobaplatin, a novel, simple, rapid and sensitive supercritical fluid chromatography with tandem mass spectrometry method was developed for the simultaneous quantitation of lobaplatin diastereoisomers in rat plasma. After a simple protein precipitation with methanol, the analytes and dexpantoprazole (internal standard) were chromatographed on an Acquity UPC2 system with a Chiralcel OZ-RH column using a mobile phase consisting of carbon dioxide and methanol (65:35, v/v) at 40°C over 6 min. The assay was linear over a concentration range of 25-15 000 ng/mL for both diastereoisomers using 100 μL of rat plasma for sample preparation. The lower limit of quantification was 25 ng/mL for both compounds, which was sufficient to detect the diastereoisomers in the incurred samples within this study. Intra- and inter-day precisions were below 11.8% and the accuracies were below 4.5%. The validated method was successfully applied to a pharmacokinetic study after an intravenous administration of 7.6 mg/kg lobaplatin to rats. There was no apparent stereospecificity in the pharmacokinetics between the two diastereoisomers of lobaplatin.
- Subjects
DIASTEREOISOMERS synthesis; ANTINEOPLASTIC agents; PLATINUM; PHARMACOKINETICS; SUPERCRITICAL fluid chromatography; THERAPEUTICS
- Publication
Journal of Separation Science, 2015, Vol 38, Issue 21, p3803
- ISSN
1615-9306
- Publication type
Article
- DOI
10.1002/jssc.201500658