Matrix effect is the effect on an analytical method caused by all other components of the sample except the specific compound to be quantified. Matrix effects and selectivity issues have long been associated with bioanalytical techniques. However the high incidence of matrix effects in liquid chromatographic tandem mass spectrometric (LC-MS-MS) methods has led to a greater understanding of the factors which contribute to these effects.A number of approaches have been investigated to improve reproducibility and robustness of LC-MS-MS methods that are subjected to matrix effect. The modifications described herein relate to instrumentation and methodological issues and include modified ionisation, ionisation switching, extraction modification and gradient high pressure liquid chromatography (HPLC) techniques and have demonstrated significantly improved robustness of complex bioanalytical methods to avoid matrix-related issues.

SummaryThe relative advantages of LC-UVand LC-MS-MS methodologies for taxol as applied to toxicokinetic and pharmacokinetic studies is reviewed and some specific applications of the two methods used in our laboratories compared. The LC-MS-MS method was found to be ~enty-five times more sensitive than the LC-UV method. In essence where plasma concentrations are high and rapid turn round of data is not required the use of the LC-UV is more than adequate. However if sensitivity is an issue, limited amounts of plasma are available and/orwhere tight deadlines are pivotal LC-MS-MS is the method of choice.