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Pharmacokinetics of cligosiban in dog plasma after oral administration by liquid chromatography electrospray ionization tandem mass spectrometry
Author(s) -
Xi Wang,
Zou Qiaogen,
Ouyang Pingkai
Publication year - 2019
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.4611
Subject(s) - chemistry , chromatography , electrospray ionization , pharmacokinetics , tandem mass spectrometry , mass spectrometry , liquid chromatography–mass spectrometry , protein mass spectrometry , electrospray , selected reaction monitoring , pharmacology , medicine
In this study, a simple and reliable liquid chromatography coupled with Q‐Exactive‐Orbitrap–MS was developed and validated for detecting and quantifying cligosiban and its metabolites in dog plasma after oral administration. The plasma samples were pretreated with acetonitrile and separated on a Diamonsil C 18 column (4.6 × 100 mm, i.d. 3 μm) with 0.1% formic acid in water and acetonitrile as mobile phase. The method was validated according to the guidance of the US Food and Drug Administration. The assay was linear over the tested concentration ranges with coefficients of correlation >0.995. The extraction recovery was >83.23% with RSD <15%. Precision was <9.31% and accuracy ranged from −4.40 to 10.20%. The method was free of matrix effects. Under the conditions used, four metabolites were detected and their identities were identified by accurate masses and fragment ions. M1 and M3 were further confirmed by reference standards. The biotransformation pathways included demethylation and glucuronidation. The validated method was further applied to quantify cligosiban, M1 and M3 in dog plasma. After oral administration, cligosiban was detectable in dog plasma and reached the maximum concentration at ~1.67 ± 0.58 h post‐dose. It was rapidly eliminated with a half‐life of 3.48 ± 0.80 h. M1 showed high plasma exposure with its area under the curve being 23.31% of that of cligosiban.