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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Gao, Ruina Zhong, Dafang Liu, Ke Xia, Yu Shi, Rongwei Li, Hua Chen, Xiaoyan |
| Description | Author Affiliation: Gao R ( Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, PR China.) |
| Abstract | Morinidazole is a new third-generation 5-nitroimidazole antimicrobial drug. To investigate the pharmacokinetic profiles of morinidazole and its major metabolites in humans, a liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous determination of morinidazole, its N-oxide metabolite (M4-1), a sulfate conjugate (M7), and two diastereoisomeric N(+)-glucuronides (M8-1 and M8-2) in human plasma. A simple acetonitrile-induced protein precipitation was employed to extract five analytes and internal standard metronidazole from 50µL human plasma. To avoid the interference from the in-source dissociation of the sulfate and achieve the baseline-separation of diastereoisomeric N(+)-glucuronides, all the analytes were separated from each other with the mobile phase consisting of 10mM ammonium formate and acetonitrile using gradient elution on a Hydro-RP C(18) column (50mm×2mm, 4µm) with a total run time of 5min. The API 4000 triple quadrupole mass spectrometer was operated under the multiple reaction-monitoring mode using the electrospray ionization technique. The developed method was linear in the concentration ranges of 10.0-12,000ng/mL for morinidazole, 1.00-200ng/mL for M4-1, 2.50-500ng/mL for M7, 3.00-600ng/mL for M8-1, and 10.0-3000ng/mL for M8-2. The intra- and inter-day precisions for each analyte met the accepted value. Results of the stability of morinidazole and its metabolites in human plasma were also presented. The method was successfully applied to the clinical pharmacokinetic studies of morinidazole injection in healthy subjects, patients with moderate hepatic insufficiency, and patients with severe renal insufficiency, respectively. |
| File Format | HTM / HTML |
| ISSN | 15700232 |
| Volume Number | 908 |
| e-ISSN | 1873376X |
| Journal | Journal of Chromatography B |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2012-11-01 |
| Publisher Place | Netherlands |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Analytical Chemistry Chromatography, High Pressure Liquid Methods Nitroimidazoles Blood Pharmacokinetics Tandem Mass Spectrometry Drug Stability Glucuronides Chemistry Humans Least-squares Analysis Oxides Renal Insufficiency Metabolism Reproducibility Of Results Sulfates Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine Analytical Chemistry Clinical Biochemistry Biochemistry |
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