HIGHLY SENSITIVE METHOD FOR THE DETERMINATION OF TAMSULOSIN HYDROCHLORIDE IN HUMAN PLASMA DIALYSATE, PLASMA AND URINE BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY ELECTROSPRAY TANDEM MASS-SPECTROMETRY

A highly sensitive method for the determination of tamsulosin hydrochl oride, a structurally new type of sulphamoile derivative, in human pla sma dialysate, plasma and urine has been developed by using liquid chr omatography-electrospray tandem mass spectrometry (LC-MS-MS). Plasma d ialysate, plasma and urine samples were extracted by brief Liquid-phas e extraction and analyzed using an HPLC system coupled to a mass spect rometer via an electrospray ionization interface. Selected reaction mo nitoring was used for the detection of tamsulosin and its internal sta ndard. This method was Validated in the concentration range 10-1000 pg /ml in plasma dialysate, 0.5-50 ng/ml in plasma, and 1-100 ng/ml in ur ine with sufficient Specificity, accuracy and precision. The in vivo p rotein binding study demonstrated that the unbound tamsulosin in human plasma obtained by the equilibrium dialysis after 0.4-mg oral dosing was measurable. Tn addition, the percentage of unbound tamsulosin in a n in vitro study (0.71-0.91%) obtained by using spiked C-14-labelled t amsulosin was slightly larger than that of the in vivo study (0.68-0.8 6%), indicating that the unbound concentration calculated by the produ ct of the plasma concentration and the in vitro unbound fraction (fu) was unfavorably overestimated. These results suggest that the combinat ion of LC-MS-MS and equilibrium dialysis method has enough sensitivity to determine the unbound concentration in clinical use and gives the concentration more exactly than the in vitro fu. (C) 1997 Elsevier Sci ence B.V.