High-performance liquid chromatographic method for the estimation of the novel investigational anti-cancer agent SR271425 and its metabolites in mouse plasma |
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| Institution: | 1. Karmanos Cancer Institute, Wayne State University, 110 East Warren, Detroit, MI 48201, USA;2. Sanofi Synthelabo Research, Malvern, PA, USA;1. Ultrasound Diagnosis Department of the Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou 646000, China;2. Department of Pharmacy of the Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou 646000, China;3. Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China;1. Department of Chemistry, Indian Institute of Technology Tirupati (IIT Tirupati), Tirupati, AP 517506, India;2. Department of Chemistry & Biochemistry, Sharda University, Greater Noida, UP 201306, India;3. Department of Chemistry, School of Natural Sciences, Shiv Nadar University, NH91, Dadri, UP 201314, India;1. School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia;2. Integrative Medicine Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, 13200 Penang, Malaysia;3. Pharmacology Department, Medical Faculty, University of Sumatera Utara, 20155 Medan, Indonesia;1. College of Pharmaceutical and Chemical Engineering, Taizhou University, Taizhou, 318000, PR China;2. School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China |
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| Abstract: | A simple and reliable HPLC method was developed for the estimation of a new anti-cancer agent that belongs to the thioxanthone class, SR271425 in mouse plasma. SR271425, it’s metabolites and internal standard (SR233377) were separated from plasma by liquid–liquid extraction using dichloromethane after quenching the plasma proteins with acetonitrile. Chromatography was performed on a reversed-phase C18 column using methanol–10 mM phosphate buffer, pH 3.5 (45:55) as mobile phase at a flow-rate of 0.8 ml/min for first 10 min and 1.4 ml/min for the next 15 min with UV–Vis detection at 264 nm and SR233377 as internal standard. The retention times of SR271425 and internal standard were 18.6 and 14.8 min, respectively. The limit of detection was 40 ng/ml and the limit of quantification was 78 ng/ml. This method was also able to detect the three metabolites of SR271425. The intra- and inter-day relative standard deviations were less than 13% at all concentrations. This analytical method was precise and reproducible for pharmacokinetics and metabolism studies of the drug in mice. SR271425 is proceeding to phase I clinical trials in 2001. |
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