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

Abstract

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 metabolization. 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 to 5000 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 3328 and 1380 ng/mL respectively (standard deviation 2267 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.

Immune modulation of effector CD4+ and regulatory T cell function by sorafenib in patients with hepatocellular carcinoma

“…Studies measuring the concentrations of sorafenib in patients with HCC after taking the approved pharmacologic dose of sorafenib (400 mg twice daily) show mean plasma concentrations that range between 3 and 6 mg/l [19, 20]. We observed a beneficial immunomodulation with sorafenib when its level is <3 mg/l.…”

Targeted therapy for human hepatic carcinoma cells using folate-functionalized polymeric micelles loaded with superparamagnetic iron oxide and sorafenib in vitro

“…The SPIONs were then removed from the redissolved micelles by magnetic field-guided accumulation. Because the chemical groups of sorafenib have a characteristic ultraviolet absorption peak at 260 nm, 18 absorbance at 260 nm was measured to determine the sorafenib content, which was calibrated using the absorption curves for various standard concentrations of sorafenib in the same mixed solvent.…”

Development and Validation of a Rapid and Simple HPLC-Uv Method for the Analysis of Sorafenib in the Presence of Polyamidoamine (Pamam) Dendrimers

“…A large inter individual variability of the values of the SFB area under the plasma concentration-time curve over 12 hr (AUC 0-12 ) was observed in the different phase I monotherapy trials. [2,4,6] There is a major problem associated with the preparation of successful sorafenib oral formulations; this drug is practically insoluble in water. A number of methodologies can be adapted to improve solubility of poorly soluble drug and further to improve its bioavailability.…”

“…SFB is currently being investigated for the treatment of other solid tumor malignancies and acute myelogenous leukemia. [1][2][3][4][5] SFB is practically insoluble in water and this feature may be responsible for inter individual variability and diverse bioavailability of SFB. The relative bioavailability of SFB is 38-49% for the tablet dosage form in comparison with an oral solution.…”