Determination of tamsulosin in human plasma by liquid chromatography/tandem mass spectrometry and its application to a pharmacokinetic study

Tamsulosin, a selective α1-adrenoceptor antagonist, is used for the treatment of benign prostatic hyperplasia (BPH). We developed and validated a rapid, sensitive, and simplified liquid chromatography analytical method utilizing tandem mass spectrometry (LC–MS/MS) for the determination of tamsulosin in human plasma. After liquid–liquid extraction with methyl t-butyl ether, chromatographic separation of tamsulosin was achieved using a reversed-phase Luna C18 column (2.0 mm × 50 mm, 5 μm particles) with a mobile phase of 10 mM ammonium formate buffer (pH 3.5)–methanol (25:75, v/v) and quantified by MS/MS detection in ESI positive ion mode. The flow rate of the mobile phase was 200 μL/min and the retention times of tamsulosin and the internal standard (IS, diphenhydramine) were 0.8 and 0.9 min, respectively. The calibration curves were linear over a range of 0.01–20 ng/mL (r > 0.999). The lower limit of quantification using 500 μL of human plasma was 0.01 ng/mL. The mean accuracy and precision for intra- and inter-day validation of tamsulosin were both within acceptable limits. The present LC–MS/MS method showed improved sensitivity for quantification of tamsulosin in human plasma compared with previously described analytical methods. The validated method was successfully applied to a pharmacokinetic study in humans.

► The more rapid, sensitive and simplified LC–MS/MS method for human plasma tamsulosin. ► A liquid–liquid sample extraction procedure without a sample-alkalinizing step. ► The lower limit of quantification using 500 μL of human plasma was 0.01 ng/mL.