Comparison of MALDI to ESI on a Triple Quadrupole Platform for Pharmacokinetic Analyses

摘要

This present work describes the systematic experimental comparison of electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI) for pharmacokinetic (PK) analysis of two drug candidates from rat plasma using single reaction monitoring (SRM) on a triple quadrupole mass spectrometer. The electrospray assay is an established method using a fast liquid chromatography (LC) separation of the sample extracts prior to mass spectrometry analysis. The novel MALDI assays measured the concentration levels of the drug candidates directly from the spotted sample extracts. Importantly, for both LC-ESI and MALDI the same solid-phase sample extraction protocol, internal standards, triple quadrupole mass analyzer platform, and SRM conditions were used, thus effectively standardizing all experimental parameters of the two assays. Initially, analytical figures of merit such as linearity, limit of quantitation, precision, and accuracy were determined from the calibration curves, indicating very similar performance for both LC-ESI and MALDI. Moreover, the LC-ESI rat plasma concentration time profiles of the drug candidates after orally dosing the animals were accurately reproduced by the MALDI assay, giving virtually identical PK results. The direct MALDI assay, however, was able to generate the data at least 50 x faster than the LC-ESI assay. It is shown in this study that analyzing the entire PK curve for one animal took less than 2 min using MALDI (with five replicate analyses per sample), whereas the corresponding LC-ESI assay required 80 min, however, allowing only two replicate measurements in that time frame.