Abstract
Sorafenib tosylate (ST) is a drug of choice for the treatment of advanced hepatocellular carcinoma. The bioavailability of ST varies from 29% to 38% due to the presence of food, medication, and other factors. Moreover, the dose of ST (400 mg twice a day) is also higher due to its poor bioavailability. Piperine is known as a natural bioenhancer, and the use of a bioenhancer ultimately leads to a synergistic effect. In this study, the development and validation of a precise, accurate, and reproducible bioanalytical method was carried out using reversed-phase high-performance liquid chromatography (RP-HPLC). The objective of the study is to determine the effect of piperine and its analogs on the pharmacokinetics of ST using rats. The dose of ST alone and in combination with piperine and its analogs, given orally to male Wistar rats in suspension form, and the drug plasma concentration was examined using a validated RP-HPLC bioanalytical method. The separation of piperine and ST was achieved on the Chromatopak basic C18 HPLC column with the dimension of 250 mm × 4.6 mm × 5 μm, guarded along with the phenomenex guard column using ACN:Water:Formic Acid (70:29.5:0.5 v/v) as the mobile phase at 280 nm (isosbestic point of piperine and ST). The pharmacokinetic data of ST, along with piperine, exhibit a significant increase in area under the curve (AUC) of ST (1.66-fold), while the two derivatives of piperine (5a and 5d) exhibited almost double the increase in AUC compared to piperine (2.58 and 2.42-fold, respectively).
Highlights
Hepatocellular carcinoma (HCC) is the fourth most commonly occurring cancer mortalities worldwide
The developed bioanalytical method was validated by following the guidelines provided by the United States Food and Drug Administration (USFDA)
The selectivity of the method was carried out to verify the interference of analytes during the method development
Summary
Hepatocellular carcinoma (HCC) is the fourth most commonly occurring cancer mortalities worldwide. HBV and HCV were found to be the major causes for cancer-related deaths globally since they lead to the progression in the hepatic damage, resulting in liver cirrhosis and HCC. Sorafenib tosylate (ST) was primarily approved to treat advanced HCC and renal cell carcinoma, the most commonly occurring cancer types in African and Asian countries (Hsu et al, 2009). ST is 4-(4-{3-[4-chloro-3-(trifluoromethyl)phenyl]uredo}phenoxy)N-2-methylpyridine-2-carboxamide 4-methyl benzenesulfonate, a multi-tyrosine kinase inhibitor given orally in the treatment of aberrant angiogenesis (Fig. 1). It bears a sturdy crystal lattice with low aqueous solubility and high lipophilicity (Log p = 3.8). There are shreds of evidence which suggests that bioavailability could be decreased by treatment with antacids, proton pump inhibitors (Herbrink, et al, 2015; Kane et al, 2006)
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