Chemically, famciclovir (FCV), known as 2-[2-(2-amino-9H-purin-9-yl)ethyl]-1,3-propanediol diacetate ( Fig. 1) is a novel antiviral drug, which is highly efficient in treatment of acute uncomplicated herpes zoster. It was reported that FCV dosed at 250 mg three times daily for 7 d was effective as 800 mg acyclovir dosed five times daily for 7 d, in the treatment of the acute signs and symptoms of herpes zoster. 1) This drug is also used for the treatment of the ophthalmic zoster.2) FCV is a synthetic guanine derivative, which is metabolized to penciclovir having the potent antiviral activity as another 9-substituted guanine derivative like acyclovir. Penciclovir is active against herpes simplex virus type 2, vericella zoster virus I, Epstein-Barr virus and hepatitis B, 3) as another 9-substituted guanine derivative like acyclovir, penciclovir is selectively phosphorylated in virus-infected cells to a monophosphate ester by thymidine kinase, followed by further phosphorylation to triphosphate ester which inhibits virus DNA polymerases. 4) Compared with acyclovir, penciclovir administration leads to higher triphosphate ester concentrations in virus-infected cells and consequently its antiviral activity persists for a longer time after removal of the compound. 4,5) FCV is absorbed rapidly and extensively after oral administration, and total systemic availability of penciclovir is 77%, 6) which is about four times higher than that of acyclovir.7) Metabolism of FCV involves sequential hydrolysis of both acetyl groups to give 6-deoxypenciclovir, which is subsequently oxidized to penciclovir, 8,9) which was synthesized by Briony Brand et al.10) FCV stability in different buffer solutions was studied by Zhang et al. 11) Since penciclovir is widely used in the antiviral therapy, it is important to develop and validate analytical methods for its determination in pharmaceutical dosage form. The HPLC method has been highly used in the quality control of drugs because of its sensitivity, reproducibility and specificity. On the other hand, the derivative UV spectrophotometric (UVDS) method is very simple, rapid, economical and allows the determination of drugs with sufficient reliability. The present work reports the development and validation of a HPLC method and a UVDS method for the estimation of FCV in tablets.
ExperimentalChemicals FCV was kindly supplied by Cipla Laboratories Ltd. (India). Pharmaceutical dosage forms (famtrex ® , varovir ® ) containing FCV was obtained commercially. Methanol, potassium dihydrogenphosphate (A.R. grade), and orthophosphoric acid (A.R. grade) were obtained from Quiligens (Mumbai, India). Ultra pure water was obtained from a Milli-Q ® UF-Plus apparatus (Millipore) and was used to prepare all solutions for the HPLC method and distilled water was used to prepare all solutions for the UVDS method. All solutions were prepared daily.Instrumentation and Analytical Conditions The HPLC method was performed on a Waters HPLC system, equipped with a model binary pump, UV dual absorbance detector (...
