Simultaneous determination of intact cisplatin and its metabolite monohydrated cisplatin in human plasma

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Vol. 772; no. 2; pp. 273 - 281
• Main Authors: Verschraagen, Miranda, van der Born, Kasper, Zwiers, T.H.Ursula, van der Vijgh, Wim J.F.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05.06.2002
• Subjects: Antineoplastic Agents - blood; Antineoplastic Agents - pharmacokinetics; Chromatography, High Pressure Liquid - methods; Cisplatin; Cisplatin - blood; Cisplatin - pharmacokinetics; Humans; Monohydrated cisplatin; Sensitivity and Specificity; Spectrophotometry, Atomic; Monohydrated cisplatin; Cisplatin
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/S1570-0232(02)00108-3

Cisplatin is a cytotoxic platinum compound, used in the treatment of several solid tumors. Cisplatin and to a greater extent its hydrolysis product monohydrated cisplatin are responsible for side-effects like nephrotoxicity. A sensitive, accurate and precise method was developed to simultaneously determine cisplatin and monohydrated cisplatin in plasma. The compounds were separated by high-performance liquid chromatography and quantified by off-line furnace atomic absorption spectrophotometry. The linear ranges for cisplatin and monohydrated cisplatin in deproteinized plasma were 60–600 and 87.5–700 n M, respectively. From plasma, the mean recovery of cisplatin was 83.2% and that of monohydrated cisplatin 79.1%. The lower limits of quantification of cisplatin and monohydrated cisplatin in deproteinized plasma were 60 and 87.5 n M, respectively. Over the whole calibration range, the within- and between-day accuracy of intact cisplatin ranged from 100.7 to 111.4 and 94.8–102.0%, respectively. The within- and between-day accuracy of monohydrated cisplatin ranged from 107.1 to 113.3 and 101.4–104.9%, respectively. The within-day and between-day precision of cisplatin ranged from 3.4 to 11.5 and 7.3–10.3%, respectively. For monohydrated cisplatin, the within-day and between-day precision ranged from 3.7 to 6.2 and 5.6–7.9%, respectively. Currently, the developed assay has been implemented in pharmacokinetic studies of patients treated with cisplatin alone or in combination with other drugs.