High-throughput analysis in drug discovery: application of liquid chromatography/ion-trap mass spectrometry for simultaneous cassette analysis of alpha-1a antagonists and their metabolites in mouse plasma

Rapid Communications in Mass Spectrometry : RCM
Z CaiA K Sinhababu

Abstract

The application of liquid chromatography/ion-trap mass spectrometry for simultaneous quantification of multiple drugs and detection of their metabolites for in vitro experiments was reported recently. In the current study, the use of these techniques was extended to in vivo pharmacokinetic (PK) studies of alpha-1a antagonists. In combination with limited time-point PK, greatly increased throughput was demonstrated for the in vivo screening and investigation of in vivo-in vitro correlation. In addition to quantitative analyses, the technique allowed simultaneous detection of major in vivo metabolites without having to reanalyze the plasma samples. The drugs were individually dosed in mice intravenously via tail vein injection and the blood samples were collected 5 min and 2 h after dosing. After the plasma samples for the different drugs had been prepared separately, they were pooled for cassette analysis. The concentrations of five test compounds in the plasma samples at 2 h ranged from 36-1062 ng/mL, whereas their 5-min plasma levels were similar. From the same cassette analysis, major metabolites in the samples were also detected simultaneously through the interpretation of full-scan mass spectra. The metabolite identificatio...Continue Reading

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Citations

May 3, 2011·Journal of Pharmaceutical and Biomedical Analysis·Tjerk BuetersSveinn Briem
Mar 6, 2009·Rapid Communications in Mass Spectrometry : RCM·Nanyan Rena ZhangWilliam Bart Emary
Mar 26, 2002·Journal of Chemical Information and Computer Sciences·György M Keseruu, László Molnár
Aug 28, 2001·Journal of Mass Spectrometry : JMS

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