Increased throughput in quantitative bioanalysis using parallel-column liquid chromatography with mass spectrometric detection.
The feasibility of quantitative bioanalysis by parallel-column liquid chromatography in conjunction with a conventional single-source electrospray mass spectrometer has been investigated using plasma samples containing a drug and its three metabolites. Within a single chromatographic run time, sample injections were made alternately onto each of two analytical columns in parallel at specified intervals, with a mass spectrometer data file opened at every injection. Thus, the mass spectrometer collected data from two sample injections into separate data files within a single chromatographic run time. Therefore, without sacrificing the chromatographic separation or the selected reaction monitoring (SRM) dwell time, the sample throughput was increased by a factor of two. Comparing the method validation results obtained using the two-column system with those obtained using the corresponding conventional single-column approach, the methods on the two systems were found to be equivalent in terms of accuracy and precision. The parallel-column system is simple and can be implemented using existing laboratory equipment with no additional capital outlays. A parallel-column system configured in this manner can be used not only for the within-a-run analysis of two samples containing two different sets of chemical entities, but also for the within-a-run analysis of two samples containing the same set of chemical entities.
Jemal
M
M
Bristol-Myers Squibb Pharmaceutical Research Institute, Bioanalytical Research, Metabolism and Pharmacokinetics, P.O. Box 191, New Brunswick, NJ 08903-0191, USA. mohammed.jemal@bms.com
Huang
M
M
Mao
Y
Y
Whigan
D
D
Powell
M L
ML
D002853:Chromatography, Liquid / Q000379:methods*; D010879:Piperazines; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013997:Time Factors; D014230:Triazoles / Q000032:analysis / Q000378:metabolism
D010879:Piperazines; D014230:Triazoles; C092333:hydroxynefazodone; C051752:nefazodone