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 |
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| Authors: | Xiangjun Meng Bo Yang Jingyi Gao Wenwen Peng Hao Wang Meiyun Shi Russell Mortishire‐Smith Yan Yang Jingkai Gu |
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| Affiliation: | 1. College of Life Science, Jilin University, Changchun, PR China;2. Waters Corporation, Wilmslow, UK |
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| 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. |
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| Keywords: | Diastereoisomers Lobaplatin Mass spectrometry Pharmacokinetics Supercritical fluid chromatography |
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