Selective LC–MS/MS determination of citalopram enantiomers and application to a pharmacokinetic evaluation of generic and reference formulations

Two methods using LC–MS/MS were validated to quantify citalopram (CTP) racemate [(R/S)‐CTP] and the enantiomers (R)‐CTP and (S)‐CTP in human plasma, respectively. Paroxetine hydrochloride was used as the internal standard, and samples were extracted by protein precipitation with acetonitrile. The non‐enantioselective method was conducted using a C18 column, and the mobile phase consisted of water for solvent A and acetonitrile for solvent B, both with 0.1% formic acid. For the chiral method, an analytical column Lux Cellulose‐1 was used. Mobile phase A was composed of water with 0.025% of formic acid and 0.05% of diethylamine, and mobile phase B consisted of acetonitrile:2‐propanol (95:5, v/v). No significant matrix effects were observed at the retention times of analytes and internal standard. The mean recovery was 89%, and the assays were linear in the concentration range of 1–50 and 5–30 ng/mL for the non‐enantioselective and enantioselective methods, respectively. The intra‐ and inter‐day precisions of both methods were less than 12.30%, and the accuracies were less than 12.13%. The validated methods were successfully applied to a pharmacokinetic study in which 20‐mg CTP tablets were administered to healthy volunteers, and their plasma levels were monitored over time in a bioequivalence study. Highlights Simple and rapid LC–MS/MS method for the quantification of citalopram and its enantiomers in human plasma. Both methods were demonstrated to be selective, reliable, and sensitive. Both methods have sufficient sensitivity to quantify the steady state through concentrations already reported for citalopram and escitalopram. Validated method presented in this study can be suitably applied to pharmacokinetic studies involving citalopram and escitalopram. Bland–Altman analysis suggested that non‐enantioselective and enantioselective methods can be applied in pharmacokinetic studies.