Quantification of levornidazole and its metabolites in human plasma and urine by ultra-performance liquid chromatography–mass spectrometry
| Autor: | Jing Zhang, Guo-ying Cao, Yu-Ran Cao, Yao-guo Shi, Yingyuan Zhang, Miao Zhao, Ji-cheng Yu, Yuancheng Chen, Bei-Ning Guo, Xiao-Jie Wu |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Chromatography Chemistry Formic acid Clinical Biochemistry Selected reaction monitoring Antiprotozoal Agents Atmospheric-pressure chemical ionization Cell Biology General Medicine Urine Mass spectrometry Biochemistry High-performance liquid chromatography Analytical Chemistry Ornidazole chemistry.chemical_compound Isomerism Limit of Detection Tandem Mass Spectrometry Liquid chromatography–mass spectrometry Humans Protein precipitation Female Chromatography Liquid |
| Zdroj: | Journal of Chromatography B. 963:119-127 |
| ISSN: | 1570-0232 |
| Popis: | We developed and validated an ultra-performance liquid chromatographic (UPLC) method coupled with atmospheric pressure chemical ionization (APCI) mass spectrometry for simultaneous determination of levornidazole and its first-pass metabolites, l-chloro-3-(2-hydroxymethyl-5-nitro-l-imidazolyl)-2-propanol (Ml), 2-methyl-5-nitroimidazole (M2) and 3-(2-methyl-5-nitro-1-imidazolyl)-1,2-propanediol (M4), in human plasma and urine. The biological samples were pretreated by protein precipitation and liquid-liquid extraction and analyzed using an ACQUITY UPLC CSH C18 column (2.1×50 mm, 1.7 μm) and a QTRAP mass spectrometer in multiple reaction monitoring mode via APCI. Acetonitrile and 0.1% formic acid in water was used as the mobile phase in gradient elution at a flow rate of 0.6 mL/min. The lower limit of quantification of this method was 0.0100, 0.00500, 0.0200 and 0.00250 μg/mL for levornidazole, M1, M2 and M4, respectively. The linear calibration curves were obtained for levornidazole, M1, M2, and M4 over the range of 0.0100-5.00, 0.00500-2.50, 0.0200-10.0 and 0.00250-1.25 μg/mL, respectively. The intra- and inter-batch precision was less than 12.2% in plasma and less than 10.8% in urine. The intra- and inter-batch accuracy was 87.8-105.7% in plasma and 92.8-109.2% in urine. The mean recovery of levornidazole, M1, M2 and M4 was 91.1-105.1%, 95.8-103.8%, 87.8-96.8%, 96.8-100.6% from plasma and 96.0-100.9%, 96.9-107.9%, 95.1-102.7%, 103.7-105.9% from urine respectively. This method was validated under various conditions, including room temperature, freeze-thaw cycles, long-term storage at -40 ± 5°C, after pretreatment in the autosampler (at 10°C), and 10- and 100-fold dilution. This newly established analytical method was successfully applied in a pharmacokinetic study following single intravenous infusion of levornidazole in 24 healthy Chinese subjects. |
| Databáze: | OpenAIRE |
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