Development of a capillary gas chromatographic procedure

A simple and fast capillary gas chromatographic method with flame ionisation detection (FID) has been developed for the analysis of fluoxetine. fluvoxamine, citalopram, sertraline and paroxetine in their pharmaceutical preparations, using clomipramine as internal standard in order to achieve quantification. The reported method is the first screening one that allows the determination of the five selective serotonin reuptake inhibitors by GC, permitting also to avoid prederivatization for the first time and it is even a pioneering work including an extensive analytical validation androbustness treatment on placebo pharmaceutical formulations too. Optimal conditions for the quantitative gas capillary separation were investigated: column head pressure (100kPa), injector and detector (FID) temperatures (210and260degreesC), time and temperature for the splitless step (0.80min and 80degreesC, respectively), volume injected (2 muL) and oven temperature program, providing analysistimes shorter than 7 min. Aspects such as stability of solutions, linearity, accuracy, precision, detection and quantitation limits are examined on a selected placebo in order to validate this method. Peak purity is assessed using mass-selective detection (DMS). The robustness of this method was evaluated using the Plackett-Burman fractional factorial experimental design with a matrix of 15 experiments and the statistical treatment proposed by Youden and Steinner. The scope of the validated method is proved in the analysis of almost existing pharmaceutical preparations, with recoveries between 98.5% and 102.4% withregard to their nominal contents. Finally, the proposed method could be also avery successfully option for the analysis of these SSRIs in real urine samples introducing a previous solid phase extraction-preconcentration step. (C) 2004 Elsevier B.V. All rights reserved.