Simultaneous selected reaction monitoring, MS/MS and MS³ quantitation for the analysis of pharmaceutical compounds in human plasma using chip‐based infusion

Abstract

An assay method with mass spectrometric detection was developed for the quantitative analysis of a pharmaceutical compound and its major metabolite in human plasma using chip-based infusion. Liquid-liquid extraction sample preparation was found to be essential to minimize matrix suppression and to achieve a limit of quantitation (LOQ) of 2.5 ng/mL using a 100 microL plasma aliquot. The potential for simultaneous quantitation in selected reaction monitoring (SRM), tandem mass spectrometry (MS/MS) (enhanced product ion), and MS(3) was investigated and found to be very beneficial in improving assay selectivity. A novel concept for monitoring quantitative assay performance using a SRM/MS(3) ratio is proposed.

Ultra-fast quantitation of saquinavir in human plasma by matrix-assisted laser desorption/ionization and selected reaction monitoring mode detection

“…This is particularly a concern for drugs which generate phase II metabolites. Nevertheless, the quantitation of pharmaceutical compounds in biological matrices without chromatographic separation using chip-based infusion has been successfully demonstrated [20,21]. With LC or infusion systems, cycle times below 10-20 s may be challenging to achieve on a routine base.…”

“…To really benefit from MALDI-SRM/MS approaches without chromatography the metabolism of the drug needs to be well characterized. A strategy to improve the selectivity of chip-based infusion assay was proposed by Leuthold et al [21] where the authors calculated a ratio between the SRM and MS 3 results. A similar set-up could also be used with the present MALDI-SRM/MS assay to check the selectivity of the analysis.…”

LC–MS-based metabonomics analysis

“…ESI-MS under nanospray conditions at sub L/min flow rates may lead to more uniform response factors. Chipbased nanoelectrospray systems [45][46][47] are another tool to reduce matrix effects and improve sensitivity [48]. APCI [49] and APPI [50] are widely used in the pharmaceutical industry, yet they are not frequently used for metabomonics investigations.…”

Development and validation of a high-throughput method for the quantitative analysis of d-amphetamine in rat blood using liquid chromatography/MS3 on a hybrid triple quadrupole-linear ion trap mass spectrometer and its application to a pharmacokinetic study

“…Very few authors reported the use of MS 3 on a hybrid quadrupole-linear ion trap mass spectrometer for the quantitative analysis of drugs in biological fluids [20,21] and, to the best of our knowledge, this appears to be the first complete validation of a quantitative method using LC-MS 3 . Herein we described, for the first time the validation of a quantitative method using fully automated protein precipitation, fast liquid chromatography and MS 3 as scan function by using a hybrid quadrupole-linear ion trap mass spectrometer.…”