Development of a high-performance liquid chromatographic method to determine the concentration of karenitecin,a novel highly lipophilic camptothecin derivative,in human plasma and urine |
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| Affiliation: | 1. Division of Pharmacy, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA;2. Pharmaceutical Development Center, Univeristy of Texas, M.D. Anderson Cancer Center, Houston, TX, USA;3. BioNumerik Pharmaceuticals, Inc, San Antonio, TX, USA;1. State Key Laboratory of Mining Response and Disaster Prevention and Control in Deep Coal Mines, Anhui University of Science and Technology, Huainan 232001, People’s Republic of China;2. School of Chemical Engineering, Anhui University of Science and Technology, Huainan 232001, People’s Republic of China;3. Wuhu Research Institute of Anhui University of Science and Technology, Wuhu 241000 People’s Republic of China;1. Sagami Chemical Research Institute, 2743-1 Hayakawa, Ayase, Kanagawa 252-1193, Japan;2. Tosoh Finechem Corp., Shiba-koen First Building 3-8-2, Shiba, Minato-ku, Tokyo 105-0014, Japan;1. Department of Food and Nutrition, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea;2. Research Institute of Human Ecology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea;3. Department of Food and Nutrition, Daejeon University, 62 Daehak-ro, Dong-gu, Daejeon 300-716, Republic of Korea;1. N.I. Lobachevsky State University of Nizhni Novgorod, Prospekt Gagarina, 23, 603950 Nizhny Novgorod, Russian Federation;2. Institute for Ultrafast Spectroscopy and Lasers, Department of Physics, The City College and Graduate School of the City University of New York, NY 10031, United States |
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| Abstract: | Karenitecin is a novel, highly lipophilic camptothecin derivative with potent anticancer potential. We have developed a sensitive high-performance liquid chromatographic method for the determination of karenitecin concentration in human plasma and urine. Karenitecin was isolated from human plasma and urine using solid-phase extraction. Separation was achieved by gradient elution, using a water and acetonitrile mobile phase, on an ODS analytical column. Karenitecin was detected using fluorescence detection at excitation and emission wavelengths of 370 and 490 nm, respectively. Retention time for karenitecin was 16.2±0.5 min and 8.0±0.2 min for camptothecin, the internal standard. The karenitecin peak was baseline resolved, with the nearest peak at 3.1 min distance. Using normal volunteer plasma and urine from multiple individuals, as well as samples from the 50 patients analyzed to date, no interfering peaks were detected. Inter- and intra-day coefficients of variance were <4.4 and 7.1% for plasma and <4.9 and 11.6% for urine. Assay precision, based on an extracted karenitecin standard plasma sample of 2.5 ng/ml, was +4.46% with a mean accuracy of 92.4%. For extracted karenitecin standard urine samples of 2.5 ng/ml assay precision was +2.35% with a mean accuracy of 99.5%. The mean recovery of karenitecin, at plasma concentrations of 1.0 and 50 ng/ml, was 81.9 and 87.8% respectively. In urine, at concentrations of 1.5 and 50 ng/ml, the mean recoveries were 90.3 and 78.4% respectively. The lower limit of detection (LLD) for karenitecin was 0.5 ng/ml in plasma and 1.0 ng/ml in urine. The lower limit of quantification (LLQ) for karenitecin was 1 ng/ml and 1.5 ng/ml for plasma and urine, respectively. Stability studies indicate that when frozen at −70°C, karenitecin is stable in human plasma for up to 3 months and in human urine for up to 1 month. This method is useful for the quantification of karenitecin in plasma and urine samples for clinical pharmacology studies in patients receiving this agent in clinical trials. |
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