Abstract
A sensitive, reliable high-performance liquid chromatography (HPLC) coupled with tandem mass spectrometry (MS/MS) method was developed for the determination of a sulfhydryl-containing compound in mouse, rat, dog, monkey and human plasma samples in support of pharmacokinetic (PK) studies. The reversed-phase chromatographic system was interfaced with an atmospheric pressure chemical ionization (APCI) source. Methyl acrylate (MA) was employed to react with the sulfhydryl group of the analyte to form a derivative that was stable in dog, monkey and human plasma at room temperature. Phenylmethylsulfonyl fluoride (PMSF), a potent inhibitor of hydrolase, was used to stabilize the test thiol-MA compound in plasma samples. Sample extracts following protein precipitation were injected into HPLC–MS/MS system. The derivatized compound was detected by a triple quadrupole mass spectrometric detector in the positive ion multiple-reaction monitoring mode. The calibration curve was linear from 2.5 to 5000 ng/ml. This paper reports the development of a HPLC–APCI/MS/MS method for the quantitative determination of a thiol component in dog plasma after derivatization with methyl acrylate derivative. The procedure was used to quantitate plasma levels following oral administration of the thiol compound to beagle dogs.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
