Sensitive gas chromatographic determination of the cyclophosphamide metabolite 2-dechloroethylcyclophosphamide in human plasma |
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| Authors: | Alwin D. R. Huitema Cindy Reinders Matthijs M. Tibben Sjoerd Rodenhuis Jos H. Beijnen |
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| Affiliation: | 1. Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Louwesweg 6, 1066 EC, Amsterdam, The Netherlands;2. Department of Medical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands;3. Division of Drug Toxicology, Faculty of Pharmacy, Utrecht University, Sorbonnelaan 16, 3508 TG Utrecht, The Netherlands;1. Key Laboratory of Industrial Biotechnology of Ministry of Education & School of Biotechnology, Jiangnan University, Wuxi 214122, PR China;2. National Key Laboratory for Food Science, Jiangnan University, Wuxi 214122, PR China;3. Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ 08854, USA;1. Rijnlands Rehabilitation Centre, Leiden, The Netherlands;2. Sophia Rehabilitation, The Hague, The Netherlands;3. Leiden University Medical Center, Leiden, The Netherlands;1. Major in Polymer Science & Engineering, School of Applied Chemical Engineering, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 41566, Republic of Korea;2. Department of Polymer Science & Engineering, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 41566, Republic of Korea, Republic of Korea;1. Center for Integrated Nanostructure Physics, Institute for Basic Science, Sungkyunkwan University, Suwon 440-746, Republic of Korea;2. Department of Energy Science, Department of Physics, Sungkyunkwan University, Suwon 440-746, Republic of Korea;3. LPICM CNRS, École polytechnique, Palaiseau 91120, France;4. School of Materials Science and Engineering, Harbin University of Science and Technology, Harbin 150040, People’s Republic of China;5. Institute of Physics, Chinese Academy of Sciences, National Centre for Nanoscience and Technology, Beijing 100080, People’s Republic of China |
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| Abstract: | Cyclophosphamide (CP) is one of the most frequently used anticancer agents. It is a prodrug requiring activation before exerting cytotoxicity. CP is deactivated to 2-dechloroethylcyclophosphamide (2-DCECP) with formation of an equimolar amount of chloroacetaldehyde. The aim of this study was to develop and validate a sensitive and simple assay for 2-DCECP in plasma of patients treated with CP. Sample pre-treatment consisted of solid-phase extraction of 500 μl of plasma over OASIS HLB (1 ml) cartridges with trofosfamide as internal standard. Separation and detection of underivatized 2-DCECP was performed with capillary gas chromatography with nitrogen/phosphorous selective detection. Extraction recovery of 2-DCECP exceeded 87%. No interference from endogenous compounds, other metabolites of CP and frequently co-administered drugs was detected. The assay was linear in the range of 5–5000 ng/ml in plasma. Accuracy, within-day and between-day precision were less than 11% for the complete concentration range. In plasma, 2-DCECP was stable for at least 1 month when kept at −70°C. Analysis of samples from patients treated with CP demonstrated the applicability of the assay. In conclusion, a sensitive and simple assay for 2-DCECP in plasma, which meets the current requirements for bioanalytical assays, was developed. |
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| Keywords: | Cyclophosphamide 2-Dechloroethylcyclophosphamide |
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