关键词: 妥洛特罗, 液相串联质谱, 人血浆, 药代动力学

Abstract:

A simple and highly sensitive method coupled with liquid chromatography-tandem quadrupole mass spectrometry (LC-MS/MS) was developed and validated for the determination of tulobuterol in human plasma. Sample was preparated by liquid-liquid extraction with i-propanol–n-hexane (5:95, v/v). Tulobuterol and tulobuterol-d9 (internal standard, IS) were separatedon a 300 Extend C₁₈ column(4.6 mm×150 mm, 5 µm), using 0.1%formic acid (A)–acetonitrile (B) (30:70, v/v) as the mobile phase at the flow rate of 1.0 mL/min with an approximately 1:1 split entering the mass spectrometer. Detection was performed by positive electrospray ionization mass spectrometry multiple reaction monitoring of the precursor-to-product ion transition of tulobuterol at m/z 228.1→m/z 154.0 and tulobuterol-d9 atm/z 237.2→m/z 154.0. The assay was linear over the range 0.01–5.0 ng/mLwith a lower limit of quantitation of 0.01 ng/mL. The intra- and inter-day precisions were 3.7% and 11.1%, respectively. Recoverywas approximately 66%, and matrix effects were minimal. This method also showed satisfactory sensitivity, specificity, and carryover. The method was successfully applied to a pharmacokinetic study of tulobuterol in healthy volunteers who were given the tulobuterol patch containing 2 mg tulobuterol.

Key words: Tulobuterol, LC-MS/MS, Human plasma, Pharmacokinetic