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

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• 作者：Dietrich A. Volmer ; Lekha Sleno ; Kevin Bateman ; Claudio Sturino ; Renata Oballa ; Timo Mauriala ; Jay Corr
• 刊名：Analytical Chemistry
• 出版年：2007
• 出版时间：December 1, 2007
• 年：2007
• 卷：79
• 期：23
• 页码：9000 - 9006
• 全文大小：266K
• 年卷期：v.79,no.23(December 1, 2007)
• ISSN：1520-6882

文摘

This present work describes the systematic experimentalcomparison of electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI) for pharmacokinetic (PK) analysis of two drug candidates from ratplasma using single reaction monitoring (SRM) on a triplequadrupole mass spectrometer. The electrospray assayis an established method using a fast liquid chromatography (LC) separation of the sample extracts prior to massspectrometry analysis. The novel MALDI assays measuredthe concentration levels of the drug candidates directlyfrom the spotted sample extracts. Importantly, for bothLC-ESI and MALDI the same solid-phase sample extraction protocol, internal standards, triple quadrupole massanalyzer platform, and SRM conditions were used, thuseffectively standardizing all experimental parameters ofthe two assays. Initially, analytical figures of merit suchas linearity, limit of quantitation, precision, and accuracywere determined from the calibration curves, indicatingvery similar performance for both LC-ESI and MALDI.Moreover, the LC-ESI rat plasma concentration timeprofiles of the drug candidates after orally dosing theanimals were accurately reproduced by the MALDI assay,giving virtually identical PK results. The direct MALDIassay, however, was able to generate the data at least 50×faster than the LC-ESI assay. It is shown in this study thatanalyzing the entire PK curve for one animal took less than2 min using MALDI (with five replicate analyses persample), whereas the corresponding LC-ESI assay required 80 min, however, allowing only two replicatemeasurements in that time frame.