Determination of tamsulosin in plasma of healthy Chinese male subjects by a novel and simple LC-MS/MS method and its application to pharmacokinetic studies

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Vol. 1229; p. 123901
• Main Authors: Zhong, Maolian, Wang, Xing, Xiong, Wenqiang, Liu, Yan, Wang, Xiaosong, Yi, Xiaoyi, Zhang, Hong
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.09.2023
• Subjects: ammonium acetate; antagonists; clinical trials; humans; hyperplasia; LC-MS/MS; liquid chromatography; males; methanol; oral administration; Pharmacokinetics; Protein precipitation method; Safety; Tamsulosin; tandem mass spectrometry; urination; LC-MS/MS; Tamsulosin; Safety; Pharmacokinetics; Protein precipitation method
• ISSN: 1570-0232; 1873-376X; 1873-376X
• DOI: 10.1016/j.jchromb.2023.123901

•A simple and rapid LC-MS/MS method was developed and validated for the quantification of tamsulosin in human plasma.•A smaller volume of plasma (100 μL) and a more economical and efficient protein precipitation method were used to achieve satisfactory sensitivity (0.05 ng/mL) and recovery.•The run time was shortened to 3.5 min, making it an attractive procedure for high-throughput bioanalysis of tamsulosin.•The bioequivalence study of a lower dosage (0.2 mg) tamsulosin hydrochloride sustained-release capsules in healthy Chinese male volunteers was first reported. Tamsulosin, the first highly selective α1-adrenoceptor antagonist, is widely used for urination disorders caused by benign prostatic hyperplasia (BPH). The pharmacokinetics and safety of 0.2 mg tamsulosin hydrochloride sustained-release capsules were evaluated in 60 healthy Chinese male subjects under fasting and fed conditions in this study. A simple, sensitive, and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of tamsulosin in human plasma, which has been applied to pharmacokinetic study. The analyte and internal standard (tamsulosin-d5) were extracted by protein precipitation, and separated on a ZORBAX Eclipse XDB-C18 column (4.6 × 50 mm,1.8 µm; Agilent Tech) using a gradient elution with mobile phases methanol and 5 mM ammonium acetate. The linear range was 0.05-15.0 ng/mL. It showed good selectivity in normal, hyperlipidemic, and hemolyzed blank matrices. The CV (%) of intra-batch precision was <4.4% and the RE (%) of accuracy was in the range of −5.0%–6.7%; the CV (%) of inter-batch precision was <−5.8% and the RE (%) of accuracy was in the range of 1.2%-4.0%. The mean extraction recovery for the analyte was 102.1 ± 3.75% and for the IS was 102.2 ± 2.00%. Two formulations were considered bioequivalent under fasting and fed conditions, and the 90% confidence intervals for the geometric mean test/reference ratios were within the predetermined range of 80%-125%. A single oral dose of 0.2 mg tamsulosin hydrochloride sustained-release capsule was well-tolerated throughout the clinical trial, and no > Grade 1 adverse events (AEs) and serious AEs occurred during the trial.