A novel approach to parallel liquid chromatography/tandem mass spectrometry
(LC/MS/MS) analyses for pharmacokinetic assays and for similar quantitativ
e applications is presented. Modest modifications render a conventional LC/
MS system capable of analyzing samples in parallel. These modifications inv
olve the simple incorporation of three valves and four LC columns into a co
nventional system composed of one binary LC pumping system, one autosampler
, and one mass spectrometer, An increase in sample throughput is achieved b
y staggering injections onto the four columns, allowing the mass spectromet
er to continuously analyze the chromatographic window of interest. Using th
is approach, the optimized run time is slightly greater than the sum of the
widths of the desired peaks. This parallel chromatography unit can operate
under both gradient and isocratic LC conditions. To demonstrate the utilit
y of the system, atorvastatin, five of its metabolites, and their deuterate
d internal standards (IS) were analyzed using gradient elution chromatograp
hy conditions. The results from a prestudy assay evaluation (PSAE) tray of
standards and quality control (QC) samples from extracted spiked human plas
ma are presented. The relative standard deviation and the accuracy of the Q
C samples did not exceed 8.1% and 9.6%, respectively, which is well within
the acceptance criteria of the pharmaceutical industry. For this particular
analysis, the parallel chromatography system decreased the overall run tim
e from 4.5 to 1.65 min and, therefore, increased the overall throughput by
a factor of 2.7 in comparison to a conventional LC/MS/MS analytical method.