Short communication
Stability indicating RP-LC determination of sildenafil citrate (Viagra) in pure form and in pharmaceutical samples

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Abstract

A simple, precise, sensitive and stability-indicating reverse-phase high performance liquid chromatographic (RP-HPLC) method has been developed for the quantitation of sildenafil citrate (SC) in pure form and its pharmaceutical formulations. Method employs water and acetonitrile (48:52 v/v) as mobile phase with flow rate of 1 ml min−1, LiChrospher C18-5 μm (25×0.46 cm) column and UV detection set at 245 nm. The internal standard method using piroxicam (PX) as the internal standard is used. The linear dynamic range of SC was found to be 0.05–7.5 μg ml−1. The proposed method is successfully employed for the determination of SC in the tablets. The excipients present in the formulations do not interfere with the assay procedure. Analytical parameters were calculated and full statistical evaluation is included.

Introduction

Sildenafil citrate (SC) or citrate salt of sildenafil is an anti-impotent drug, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). SC is chemically designated as 1-[[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazole [4,3-d] pyrimidin-5-yl)-4-ethoxyphenyl]sulfonyl]-4-methylpiperazine citrate. The activity of sildenafil as an efficacious, orally active agent for the treatment of male erectile dysfunction has been reported by many authors [1], [2], [3]. No official (pharmacopoeial) method has been found for the assay of SC formulations. However, Cooper et al. [4] developed an assay procedure for the simultaneous estimation of sildenafil and its metabolite in plasma using automated sequential trace enrichment of dialysates and high performance liquid chromatography. Indravadan et al. [5] described a reverse-phase high performance liquid chromatographic (HPLC) method for the determination of SC in plasma, and Segall et al. [6] reported RP-HPLC method for the determination of SC in the presence of its oxidative-induced degradation products. Mohammed [7] reported a stability-indicating HPLC method for the determination of SC in pharmaceutical preparations and its application to kinetic studies. Miao et al. [8] reported an RP-HPLC method for the determination of SC and its related compound in tablets. Altokka et al. [9] described a Flow Injection Analysis (FIA) method for the determination of SC using UV detection. Daraghhmeh et al. [10] reported HPLC method for the determination of SC and related substances in the commercial products and tablet dosage form. However, all the reported HPLC methods are critical of the pH of the mobile phase used.

Present communication, which describes the RP-HPLC assay procedure exclusively for SC in pure form and in formulations, is simple, precise and sensitive. Present method uses simple mobile phase without the need of buffer, involves no complex procedure to prepare sample solutions [5], [8], and offers better sensitivity than some of the reported methods [5], [7], [8]. Also, present assay procedure employs internal standard method with piroxicam (PX) as internal standard. It is known that an internal standard, if properly chosen and used, can compensate for several types of both random and systematic errors. The internal standard should provide a signal that is similar to the analyte signal in most ways but sufficiently different so that the two signals are readily distinguishable by the instrument. It is interesting to note that PX itself, an important anti-inflammatory drug, can effectively be used as internal standard for the analysis of SC.

Section snippets

Instrumentation and reagents

A Merck-Hitachi 7000 series low pressure gradient HPLC system equipped with an L7100 low pressure quaternary gradient pump, L7612 solvent degasser, a Rheodyne model 7125 injection valve with a fixed loop of 20 μl and Merck-Hitachi L7400 multiwavelength UV–Vis detector was used. The analyte peaks were resolved on a LiChrospher C18-5 μm (25×0.46 cm) column. A PC-based Winchrom chromatographic software condition was used for data integration.

SC and PX were obtained as gift samples from Sun

Optimization of the variables

Optimum conditions, which are necessary for the quantitative analysis of the drug with maximum sensitivity, were established by a number of preliminary experiments. Optimum conditions were fixed by varying one parameter at a time by fixing other parameters constant and observing its effect on the response factor and also on the peak resolution. Effect of wavelength on the response factor and on the peak resolution was observed over the wavelength range 230–260 nm. 245 nm±2 unit was found to be

Conclusions

The results of the proposed HPLC method showed that the data are consistent with the label claim of the formulations. The calibration curve showed linear response over the range of concentration used in the assay procedure. The lower value of RSD for the reproducibility studies and recovery studies shows that the method is precise and accurate. Further, there is no interference of the excipients used in the formulations. The present RP-HPLC method uses simple mobile-phase water and acetonitrile

Acknowledgements

One of the authors (N.D.D) thanks Adhichunchanagiri Institute of Technology (AIT), Chickmagalur and All India Council for Technical Education (AICTE), New Delhi for the financial support to this research work under the project 8017/RD II/MON-SW/653/R&D/(98–99)/2000.

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