Development and Validation of Liquid Chromatographic and UV Derivative Spectrophotometric Methods for the Determination of Famciclovir in Pharmaceutical Dosage Forms

Abstract

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 (...

Stability‐indicating methods for the determination of famciclovir in the presence of its alkaline‐induced degradation product

“…The intraday precision was assessed from the results of three replicate analyses of pure FCV on a single day. [6] The calculated t-and F-values are less than the theoretical ones indicating that there is no significant difference between the proposed methods and the reported method [6] with respect to accuracy and precision. The results of intra-day and inter-day precisions are illustrated in Table 4.…”

“…One-way ANOVA was applied for the comparison of those methods, where there was no significant difference between the proposed methods and the reported method [6] (Table 6). …”

“…This HPLC method has an advantage over the reported HPLC method, [6] being a stability-indicating method, while the reported HPLC is not because both the intact drug and its alkaline degradation product have the same retention time and their peaks are overlapped on each other. The robustness of the HPLC method was investigated by the analysis of samples under a variety of experimental conditions, such as small changes in the pH (3.0-3.5) and small changes in proportions of different components by up to ±0.5% mainly of the organic part of the mobile phase, plus the ionic strength of the phosphate salt component.…”

“…[4] Metabolism of FCV involves sequential hydrolysis of both acetyl groups to give 6deoxypenciclovir, which is subsequently oxidized to penciclovir. These methods include derivative method, [6] colorimetric methods using Tpooo (benzene sulfonic acid), [7] Folin's reagent and resorcinol, [8] bromocresol green, bromothymol blue, bromocresol purple and bromophenol blue, [9] 2,6-dichloroquinone chlorimide, [10] high performance liquid chromatographic (HPLC) methods, [6,11 -15] capillary electrophoresis, [16] electrochemical method [17] and electro-spray ionization mass spectrometry. Few methods have been reported for the quantitative estimation of FCV in pharmaceutical formulations and in body fluids.…”

Development and validation of high-throughput liquid chromatography–tandem mass spectrometric method for simultaneous quantification of loratadine and desloratadine in human plasma

“…Linearity means that the assay provides test results that are proportional to the concentration of the analyte in the sample with directly or via a mathematical transformation [23]. The relationship between the experimental response value and known concentrations of the analyte is referred to as calibration curve.…”