Dihydroxybutylether (DHBE), a strong choleretic drug, is a mixture of three regioisomers: 4-(3-hydroxybutoxy)-2-butanol (I), 3-(4-hydroxy-2-butoxy)-1-butanol (II) and 3-(3-hydroxylbutoxy)-1-butanol (III). A liquid chromatography-tandem mass spectrometry method was developed and validated for the quantification of dihydroxybutylether (DHBE) regioisomers in human plasma. After plasma samples were deproteinized with 10% perchloric acid, the post-treatment samples were analyzed on a Capcell Pak C-18 MGII column interfaced with a triple quadrupole tandem mass spectrometer in positive electro-spray ionization mode. Methanol and water was used as the mobile phase with a gradient elution at a flow rate of 1 mL/min. Acetaminophen was used as an internal standard (IS). Multiple selected reaction monitoring was performed using the transitions m/z 163 -> 55 and m/z 152 -> 110 to quantify DHBE regioisomers and IS, respectively. Five DHBE isomers (a, b, c, d and e) were separated under the present chromatographic condition. The assay was linear over the concentration range of 5.0-200 ng/mL for DHBE isomers a, b and c, and 10.0-400 ng/mL for DHBE isomers d and e. The intra- and inter-day precision was within 13.6% in terms of relative standard deviation (RSD%) and the accuracy within 7.3% in terms of relative error. This simple and sensitive and easily reproducible LC-MS/MS method was successfully applied to the pharmacokinetic study of DHBE regioisomers in healthy male Chinese volunteers after an oral dose of 1.0 g DHBE. (C) 2012 Elsevier B.V. All rights reserved.
