title: Development and validation of a LC-MS/MS method for the quantification of the regioisomers of dihydroxybutylether in human plasma.
abstract: 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 electrospray ionization mode. Methanol and water was used as the mobile phase with a gradient elution at a flow rate of 1mL/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 5.0-200ng/mL for DHBE isomers a, b and c, and 10.0-400ng/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 1.0g DHBE.
authors.affiliation: Department of Pharmaceutical Analysis, Pharmacy School, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yuan
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Yao
authors.initials: Y
authors.lastname: Fu
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.forename: Lixin
authors.initials: L
authors.lastname: Guo
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xu
mesh_terms: D000082:Acetaminophen / Q000737:chemistry; D001800:Blood Specimen Collection; D011232:Chemical Precipitation; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D004987:Ethers / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D000432:Methanol / Q000737:chemistry; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013696:Temperature; D014867:Water / Q000737:chemistry
chemical_list: D004987:Ethers; D014867:Water; D000082:Acetaminophen; C000987:4,4'-oxydi-2-butanol; D000432:Methanol