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Quantitative determination of duloxetine and its metabolite in rat plasma by HPLC‐MS/MS
Author(s) -
Chae Jungwoo,
Baek Hyunmoon,
Kim Sang Kyum,
Kang Hoil,
Kwon Kwangil
Publication year - 2013
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.2895
Subject(s) - chemistry , chromatography , duloxetine , metabolite , protein precipitation , triple quadrupole mass spectrometer , selected reaction monitoring , mass spectrometry , glucuronide , electrospray ionization , tandem mass spectrometry , high performance liquid chromatography , duloxetine hydrochloride , biochemistry , medicine , alternative medicine , pathology
The major metabolite of duloxetine is a glucuronide conjugate of 4‐hydroxy duloxetine (4‐HD). However, interestingly, there have been no reports determining concentrations of 4‐HD and no fully validated method has been established for measuring duloxetine and 4‐HD in rat plasma. We developed a method for the simultaneous quantification of duloxetine and its metabolite in rat plasma using high‐performance liquid chromatography tandem mass spectrometry. Duloxetine and 4‐HD were analyzed on a reverse‐phase C 18 analytical column after protein precipitation of the plasma sample with methanol, using carbamazepine as an internal standard. The isocratic mobile phase of 5 m m ammonium acetate–methanol (4:6, v/v) was eluted at 0.4 mL/min. Quantification was performed on a triple‐quadrupole mass spectrometer using electrospray ionization, and the ion transition monitored in selective reaction monitoring mode. The coefficient of variation for assay precision was <18.0%, and the accuracy was 84.0–118.0%. This method was successfully used to measure the concentrations of duloxetine and its metabolite in plasma following the oral administration of a single 40 mg/kg dose in rats. Copyright © 2013 John Wiley & Sons, Ltd.