Quantitative determination of unchanged cisplatin in rat kidney and liver by high-performance liquid chromatography |
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| Institution: | 1. National Centre of Excellence in Analytical Chemistry, University of Sindh, Jamshoro 76080, Pakistan;2. Dr M.A. Kazi Institute of Chemistry University of Sindh, Jamshoro 76080, Pakistan;1. Department of Pharmaceutics, National Organization for Drug Control and Research, Giza, 12654, Egypt;2. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, Egypt;1. Shanghai Key Laboratory of Functional Materials Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai, 200237, PR China;2. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, PR China;1. Dipartimento di Chimica e Tecnologie del Farmaco, “Sapienza” University of Rome, P.le Aldo Moro 5, 00185 Roma, Italy;2. Dipartimento di Ingegneria Civile e Ambientale, Università di Perugia and ISTM-CNR, Via Duranti 93, 06125 Perugia, Italy;1. Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad Universitaria, CDMX., C.P. 04510, Mexico;2. Facultad de Ciencias Químicas, Universidad Autónoma de Chihuahua. Circuito Universitario S/N, Chihuahua, Chihuahua C. P. 31125. Mexico |
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| Abstract: | A quantitative analytical method for measuring unchanged cisplatin (CDDP) and high- and low-molecular-mass metabolites (fixed and mobile metabolites) in rat kidney and liver was developed. Unchanged CDDP, separated from fixed and mobile metabolites in tissue homogenates by consecutive procedures of fractionation and ultrafiltration, was determined by high-performance liquid chromatography (HPLC) with post-column derivatization. Although unchanged CDDP was found to be partly metabolized to fixed metabolites during the preparation of cytosolic ultrafiltrates, the recovery of unchanged CDDP gave a constant value (about 70%), which was independent of tissue type and CDDP concentration (from 1 to 10 μg/ml). The detection limit for unchanged CDDP in the cytosolic ultrafiltrate was 20 ng/ml, corresponding to a concentration detection limit of 65 ng Pt per g of tissue in the kidney and liver. The concentrations of fixed and mobile metabolites were determined as platinum concentrations in the tissue homogenate and in the cytosolic ultrafiltrate using atomic absorption spectrometry after correcting for transformation of unchanged CDDP to fixed metabolites. The distribution of unchanged CDDP, mobile metabolites and fixed metabolites in rat kidney and liver, after bolus injection of CDDP (5 mg/kg), was determined using this method. |
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