Determination of sofosbuvir with two co-administered drugs;paracetamol and DL-methionine by two chromatographic methods. Application to a pharmacokinetic study

摘要

Aim: Two rapid and sensitive chromatographic methods have been developed and validated for simultaneous analysis of sofosbuvir (SOF) in rat plasma with two co-administered drugs, paracetamol (PAR) and DL-methionine (MET). Materials & methods: The first method relied on using TLC-densitometry with a developing system consisted of chloroform: methanol: glacial acetic acid: formic acid in the ratio of 9.5: 1: 1.5: 0.5, by volume. The studied analytes and the internal standard naphazoline hydrochloride were scanned at 210nm. The second method was HPLC method, whereas the analytes and the internal standard cinnarizine were separated on XTerra((R)) HPLC RP C18 column using gradient elution mode and a mobile phase consisted of methanol: 0.1% aqueous TEA at pH 3 adjusted with orthophosphoric acid at 210nm. Results: The TLC-densitometry method showed linearity over concentration ranges of 160-3000ng/band for SOF and PAR, 300-3000ng/band for MET, but HPLC method was linear and validated over concentration ranges of 150-5000ng/ml for SOF, 300-5000ng/ml for both PAR and MET. Conclusion: All validation parameters met the acceptance criteria according to US FDA guidelines. Pharmacokinetic study was successfully applied and proved the possibility of co-administration of SOF with PAR and MET.