Development and validation of a highly sensitive and selective LC-MS/MS method for the determination of 15-hydroxylubiprostone in human plasma: application to a pharmacokinetic study in healthy Chinese volunteers

Abstract

1. 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.

2. 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.

3. 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.

4. 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.

Keywords:

• 15-hydroxylubiprostone
• LC-MS/MS
• prostaglandin
• pharmacokinetics
• liquid-liquid extraction

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This academic research was financially supported by the National Natural Science Foundation of China [grant number: 82173780], Jiangsu Provincial Natural Science Foundation [grant number: BK20191322] as well as the Open Project Program of MOE Key Laboratory of Drug Quality Control and Pharmacovigilance [grant number: DQCP20/21MS04].