Quantitative determination of ketoconazole by UPLC-MS/MS in human plasma and its application to pharmacokinetic study.
In this study, a simple, rapid and sensitive ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method is described for determination of ketoconazole (KTZ) in human plasma samples using carbamazepine as the internal standard (IS). Sample preparation was accomplished through one-step liquid-liquid extraction by ethyl acetate, and chromatographic separation was performed on an Acquity BEH C18 column (2.1 mm×50 mm, 1.7 μm) with gradient profile at a flow of 0.45 mL/min. Mass spectrometric analysis was performed using a QTrap5500 mass spectrometer coupled with an electro-spray ionization (ESI) source in the positive ion mode. The MRM transition of m/z 531.2→489.3 was used to quantify for KTZ. The linearity of this method was found to be within the concentration range of 5-15 000 ng/mL for KTZ in human plasma. Only 1.5 min was needed for an analytical run. The method herein described was superior to previous methods and was successfully applied to the pharmacokinetic study of KTZ in healthy Chinese volunteers after oral administration.
Wenzhou People's Hospital, Wenzhou, China.
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ML
Hu
Wenzhou People's Hospital, Wenzhou, China.
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M
Xu
The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
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Ye
D000085:Acetates / Q000737:chemistry; D000284:Administration, Oral; D000935:Antifungal Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D044466:Asian People; D002138:Calibration; D002214:Capsules; D002681:China; D002853:Chromatography, Liquid / Q000379:methods* / Q000592:standards; D064368:Healthy Volunteers; D006801:Humans; D007654:Ketoconazole / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D016014:Linear Models; D059625:Liquid-Liquid Extraction; D012015:Reference Standards; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000592:standards; D053719:Tandem Mass Spectrometry / Q000592:standards
D000085:Acetates; D000935:Antifungal Agents; D002214:Capsules; C007650:ethyl acetate; D007654:Ketoconazole