FDA-Validated Ecofriendly Chromatographic Methods for Simultaneous Determination of Gemcitabine and Sorafenib: Applications to Pharmacokinetics

Abstract

AbstractCombination therapy of gemcitabine and sorafenib is synergistically effective and well tolerated in patients with non-small cell lung cancer (NSCLC). In this study, the pharmacokinetic parameters of both gemcitabine and sorafenib were estimated after intra-peritoneal administration in rats using novel, green and sensitive RP-HPLC and TLC-densitometric methods where sildenafil used as an internal standard. Firstly, the developed RP-HPLC method achieved on ZORBAX Eclipse Plus C18 (4.6 mm × 150 mm, 5 μm) using a mixture of methanol: 40 mM ammonium acetate solution. On the other hand, the developed TLC-densitometric method was achieved on TLC plates using a developing system of methanol: ethyl acetate (3: 7, by volume) and scanning wave length at 260 nm. Additionally, the developed methods were validated according to FDA guidelines. Moreover, the developed methods were successfully used to study the pharmacokinetic parameters of both gemcitabine and sorafenib after administration of each drug alone and co-administration in rats. The results presented that drug–drug interaction between drugs happened when administrated together affecting the pharmacokinetic parameters of each other. The proposed methods, being ecofriendly, accurate, and sensitive, may become the corner stone for further clinical studies of the studied drugs determinations applied on humans.