Xianjing Li, Haitao Yu, Wenjing Guo
Jun 3, 2022
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Quality indicators
Journal
Xenobiotica
Abstract
Abstract Lubiprostone, a derivative of prostaglandin E1, is the first chemical-type constipation treatment approved by FDA. Lubiprostone has low systemic exposure after oral administration. Therefore, it is recommended that 15-hydroxylubiprostone, which is a dominant active metabolite of lubiprostone, be used as the pharmacokinetic evaluation indicator. Due to the microdosage of the lubiprostone capsules, it is difficult to develop a highly sensitive bioanalytical method for 15-hydroxylubiprostone. In this study, a highly sensitive and selective liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) method has been established and fully validated for the quantification of 15-hydroxylubiprostone in human plasma, and the validated bioanalytical method has been applied to a pharmacokinetic study of lubiprostone capsules successfully. The pharmacokinetics of 15-hydroxylubiprostone were observed after fed administration in healthy Chinese volunteers. The C max and AUC 0-t were 75.8 ± 57.6 pg/mL and 222 ± 68.0 pg·h/mL for 15-hydroxylubiprostone. This study investigated the pharmacokinetic properties of 15-hydroxylubiprostone under fed conditions in healthy Chinese volunteers and would provide clinical guidance for the application and further development of lubiprostone capsules.