Application of LC-SIM-MS in drug assay development

Sensitive and selective HPLC procedures with single quadrupole mass spectrometric detection have been developed for use in animal plasma samples. Sensitivities of 1–2 ng mL−1 could be obtained within reasonably short development times. Straightforward sample preparation procedures (protein precipitation, followed by either direct injection or column switching procedure) gave high sample throughput. Deuterated analogues of the analytes were used as internal standards. A drawback (as compared to HPLC-UV) is the more limited linear dynamic range. As a consequence, plasma samples from high dose toxicological studies had to be diluted prior to the sample preparation step to fall into the linear concentration range. The procedures have been applied to hundreds of plasma samples from various non-clinical studies.