Comparison of Packed-Column Supercritical Fluid Chromatography-Tandem Mass Spectrometry with Liquid Chromatography-Tandem Mass Spectrometry for Bioanalytical Determination of (R)- and (S
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- 作者：Steven H. Hoke ; II ; J. David Pinkston ; Ruth E. Bailey ; Suzanne L. Tanguay ; and Thomas H. Eichhold
- 刊名：Analytical Chemistry
- 出版年：2000
- 出版时间：September 1, 2000
- 年：2000
- 卷：72
- 期：17
- 页码：4235 - 4241
- 全文大小：208K
- 年卷期：v.72,no.17(September 1, 2000)
- ISSN：1520-6882
文摘
The popularity of packed-column supercritical fluid, subcritical fluid, and enhanced fluidity liquid chromatographies (pcSFC) for enantiomeric separations has increasedsteadily over the past few years. The addition of asignificant amount (typically 20-95%) of a viscositylowering agent, such as carbon dioxide, to the mobilephase provides a number of advantages for chiral separations. For example, higher mobile-phase flow rates canoften be attained without a concomitant loss in chromatographic efficiency since diffusion coefficients, and optimum velocities, are typically higher in pcSFC. Ultratraceenantioselective quantitation of drugs in biomatrixes isan ideal application for these chromatographic attributes.To demonstrate the utility of this approach, a pcSFCtandem mass spectrometry (pcSFC-MS/MS) method wascompared to a LC-MS/MS method for quantitation of the(R)- and (S)-enantiomers of ketoprofen (kt), a potentnonsteroidal, anti-inflammatory drug, in human plasma.After preparation using automated solid-phase extractionin the 96-well format, kt enantiomers were separated ona Chirex 3005 analytical column using isocratic conditions. Validation data and study sample data from patientsdosed with either orally or topically administered ketoprofen were generated using both pcSFC and LC as thechromatographic methods to compare and contrast theseanalytical approaches. Generally, most analytical attributes, including specificity, linearity, sensitivity, accuracy, precision, and ruggedness, for both of thesemethods were comparable with the exception that thepcSFC separation provided a roughly 3-fold reduction inanalysis time. A 2.3-min pcSFC separation and a 6.5-minLC separation provided equivalent, near-baseline-resolvedpeaks, demonstrating a significant time savings for analysis of large batch pharmacokinetic samples using pcSFC.