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.
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 UPC(2) 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.
authors: College of Life Science, Jilin University, Changchun, PR China.
authors: Xiangjun
authors: X
authors: Meng
authors: College of Life Science, Jilin University, Changchun, PR China.
authors: Bo
authors: B
authors: Yang
authors: College of Life Science, Jilin University, Changchun, PR China.
authors: Jingyi
authors: J
authors: Gao
authors: College of Life Science, Jilin University, Changchun, PR China.
authors: Wenwen
authors: W
authors: Peng
authors: College of Life Science, Jilin University, Changchun, PR China.
authors: Hao
authors: H
authors: Wang
authors: College of Life Science, Jilin University, Changchun, PR China.
authors: Meiyun
authors: M
authors: Shi
authors: Waters Corporation, Wilmslow, UK.
authors: Russell
authors: R
authors: Mortishire-Smith
authors: College of Life Science, Jilin University, Changchun, PR China.
authors: Yan
authors: Y
authors: Yang
authors: Research Center for Drug Metabolism, Jilin University, Changchun, PR China.
authors: Jingkai
authors: J
authors: Gu
mesh_terms: D000818:Animals; D019540:Area Under Curve; D025924:Chromatography, Supercritical Fluid / Q000379:methods*; D003503:Cyclobutanes / Q000097:blood* / Q000493:pharmacokinetics; D006207:Half-Life; D057230:Limit of Detection; D009944:Organoplatinum Compounds / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D015203:Reproducibility of Results; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D003503:Cyclobutanes; D009944:Organoplatinum Compounds; C066228:lobaplatin
keywords: Diastereoisomers; Lobaplatin; Mass spectrometry; Pharmacokinetics; Supercritical fluid chromatography