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Cancer Chemother Pharmacol. 2011 Jul;68(1):239-45. doi: 10.1007/s00280-010-1474-y. Epub 2010 Oct 7.

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

Author information

1
Department of Internal Medicine II, University of Würzburg Medical Centre, Oberdürrbacher Str. 6, 97080 Würzburg, Germany. Heinz_W@klinik.uni-wuerzburg.de

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.

PMID:
20927524
DOI:
10.1007/s00280-010-1474-y
[Indexed for MEDLINE]

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