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High-performance liquid chromatographic method for the determination of sorafenib in human serum and peritoneal fluid

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Abstract

Purpose

Sorafenib is recommended for therapy of advanced hepatocellular carcinoma and renal cell carcinoma. Preclinical data indicate a relation between dose and antitumor efficacy. In clinical trials, adverse events improve after dose reduction suggesting a dose-dependent toxicity. Given dose has a direct impact on the drug serum concentration, but the latter also can be influenced by multiple factors, including interaction and metabolisation. To enable the investigation of concentration-related effects, an easy and sensitive assay for sorafenib drug monitoring is essential.

Methods

A high-performance liquid chromatography (HPLC) analysis involving an extraction with diethyl ether followed by separation on a Pinnacle™ DB C18 column and quantitation by UV absorbance at 260 nm was established. Sorafenib concentrations in samples of serum and peritoneal fluid have been determined.

Results

The assay was validated for serum samples and is linear over the concentration range of 100–5,000 ng/ml with a determination coefficient of >0.999. The limit of detection is 0.25 ng/ml. The intra- and inter-day coefficients of variation were below 3.03%. Sorafenib recovery in spiked probes of peritoneal fluid was above 85%. Sorafenib concentrations in 44 serum samples and 14 probes of peritoneal fluid have been determined with a mean of 3,328 and 1,380 ng/ml, respectively (standard deviation 2,267 and 659 ng/ml).

Conclusions

A sensitive and selective HPLC method for the determination of sorafenib in human serum was developed and also verified for peritoneal fluid. This method provides a useful tool for pharmacokinetic investigations as well as for therapeutic drug monitoring of sorafenib.

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Acknowledgments

This work was supported by the German Federal Ministry of Economics and Technology (BMWi) and the European Social Fund (ESF), Project no. 03EGSBY044.

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Authors and Affiliations

  1. Department of Internal Medicine II, University of Würzburg Medical Centre, Oberdürrbacher Str. 6, 97080, Würzburg, Germany

    Werner J. Heinz, Kathrin Kahle, Annegret Helle-Beyersdorf, Diana Schirmer, Ulrike Lenker, Daniela Keller, Peter Langmann & Hartwig Klinker

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  1. Werner J. Heinz
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  2. Kathrin Kahle
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Correspondence to Werner J. Heinz.

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Heinz, W.J., Kahle, K., Helle-Beyersdorf, A. et al. High-performance liquid chromatographic method for the determination of sorafenib in human serum and peritoneal fluid. Cancer Chemother Pharmacol 68, 239–245 (2011). https://doi.org/10.1007/s00280-010-1474-y

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  • DOI: https://doi.org/10.1007/s00280-010-1474-y

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