The feasibility of quantitative MALDI versus ESI on a triple quadrupole platform for PK analysis of drugs

摘要

To demonstrate the application of a novel quantitative MALDI technique as a potential replacement of electrospray LC/MS for high-speed PK analyses of drugs MALDI-MS is usually applied for qualitative measurements of biopolymers. Quantitative applications are complicated as non-homogeneous co-crystallization of analyte and MALDI matrix leads to irreproducible analyte signals. Small molecules are even more difficult to analyze because of strong interferences from matrix ions in the low mass range. Specific precursor/product ion combinations from MS/MS experiments, however, can circumvent these background signals. Importantly, MALDI achieves a high sample throughput in combination with a triple quadrupole MS, allowing dedicated MRM experiments and, coupled with a high-frequency laser, generating a large number of spectra for improved precision. This presentation describes the systematic comparison of MALDI versus ESI on triple quadrupole MS for PK analyses of rat plasma, utilizing identical sample preparation conditions for both assays.