Validation of a capillary gas chromatographic method for the determination of Sildenafil Citrate in its pharmaceutical formulations (Viagra). Experimental design for evaluating the ruggedness of the method

摘要

A simple and rapid method was developed for the analysis of Sildenafil Citrate (Viagra) in its pharmaceutical formulations (Viagra 25, 50 and 100 mg) in the presence of excipients, using its metabolite UK-103, 320 as internal standard for quantification. The optimal separation conditions were established in presence of all compounds in the pharmaceutical formulations and provided analysis times of less than 12 minutes. The conditions were: column head pressure (110 KPa), injector and flame ionisation detector (FID), temperatures (325 and 300°C), time and temperature for the splitless step (0.75 min and 70°C), sample size (2μl) and an oven temperature program. Aspects such as stability of the solutions, linearity, accuracy, reproducibility, specificity, limits of detection (LODs) and of quantification (LOQs) are examined in order to validate the method in presence of all excipients. Some of these aspects such as specificity were also assessed by mass spectrometric detection in the SCAN mode. A ruggedness test of this method was made using the fractional factorial model of Plackett-Burman. In our case, this involved designing a matrix of 15 experiments in which the influence of the seven factors mentioned above was tested at three different levels on different chromatographic results such as resolution, efficiency, relative peak areas, etc. The chromatographic results were evaluated statistically by the method of Youden and Steiner. The highly satisfactory results obtained in both the validation and ruggedness tests show that the CG method could be a very valuable option as an official method for the determination of Sildenafil Citrate in its pharmaceutical formulations.