Effect of the sample matrix on the determination of indinavir in human urine by HPLC with turbo ion spray tandem mass spectrometric detection

The HPLC/tandem mass spectrometric (LC/MS/MS) behavior of indinavir, an HIV protease inhibitor, in human urine is presented as an example of a case wh ere endogenous matrix components were found to interfere with the ionizatio n of the target analyte. The MS/MS system used for these experiments was eq uipped with a turbo ion spray LC interface. Results from two sample prepara tion procedures (direct dilution of urine vs urine extraction) and two chro matographic systems (low vs. high capacity factor (k')) for the analytes we re compared. Additionally, the precision of the analysis that was achieved while using a stable isotope labeled internal standard is contrasted with t he results obtained using an analog of indinavir as internal standard. The results obtained indicated that during development and validation of LC/MS/ MS based assays the potential effect of co-eluting 'unseen' endogenous spec ies should be evaluated to ensure that sample preparation and chromatograph y is adequate to overcome the matrix effect problems. (C) 1998 Elsevier Sci ence B.V. All rights reserved.