Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
7614867 | Journal of Chromatography B | 2018 | 7 Pages |
Abstract
Sulprostone is a potent prostaglandin E2 (PGE2) analogue and one of the first identified selective G-protein-coupled receptor 3 (EP3) agonists. It has been investigated as a potential antiulcer agent and frequently used in the research of EP3 antagonist. To assist pharmacokinetic and pharmacodynamic studies, a rapid and sensitive LC-MS/MS method was developed and qualified for the quantitation of sulprostone in monkey plasma. Using electrospray ionization mass spectrometry, an ammonium adduct in positive mode was chosen for analysis which had seven times of the sensitivity of the depronated ion in negative mode. Latanoprost, a prostaglandin F2α analogue, was used as the internal standard while good sensitivity and chromatography were obtained on a 2.6â¯Î¼m core-shell column with pentafluorophenyl stationary phase. An assay dynamic range of 2 to 4000â¯ng/mL was achieved with a sample volume of 25â¯Î¼L plasma on a Sciex API4000 instrument with simple protein precipitation. Several esterase inhibitors including sodium fluoride (NaF), phenylmethanesulfonyl fluoride (PMSF), diisopropylfluorophosphate (DFP), paraoxon and dichlorvos as well as wet ice conditions were explored for the stabilization of sulprostone in monkey plasma. The developed method was successfully applied for the evaluation of pharmacokinetics of sulprostone after intravenous administration of 0.5â¯mg/kg to cynomolgus monkey.
Related Topics
Physical Sciences and Engineering
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Analytical Chemistry
Authors
Yifan Shi, Matthew M. Rankin, Lisa D. Norquay, Naidong Weng, Shefali Patel,