Development of a capillary gas chromatographic procedure

Abstract

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 and robustness treatment on placebo pharmaceutical formulations too. Optimal conditions for the quantitative gas capillary separation were investigated: column head pressure (100 kPa), injector and detector (FID) temperatures (210 and 260 °C), time and temperature for the splitless step (0.80 min and 80 °C, respectively), volume injected (2 μL) and oven temperature program, providing analysis times 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% with regard to their nominal contents. Finally, the proposed method could be also a very successfully option for the analysis of these SSRIs in real urine samples introducing a previous solid phase extraction-preconcentration step.