Development and validation of stability indicating method for determination of sertraline following ICH guidlines and its determination in pharmaceuticals and biological fluids

Background Sertraline is a well known antidepressant drug which belongs to a class called selective serotonin reuptake inhibitor. Most published methods do not enable studying the stability of this drug in different stress conditions. Results Two new methods were developed for the determination of sertraline (SER). Both methods are based on coupling with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) in borate buffer of pH 7.8 and measuring the reaction product spectrophotometrically at 395 nm (Method I) or spectrofluorimetrically at 530 nm upon excitation at 480 nm (Method II). The response-concentration plots were rectilinear over the range 2-24 μg/mL and 0.25-5 μg/mL for methods I and II respectively with LOD of 0.18 μg/mL and 0.07 μg/mL, and LOQ of 0.56 μg/mL and 0.21 μg/mL for methods I and II, respectively. Conclusion Both methods were applied to the analysis of commercial tablets and the results were in good agreement with those obtained using a reference method. The fluorimetric method was further applied to the in vivo determination of SER in human plasma. A proposal of the reaction pathway was presented. The spectrophotometric method was extended to stability study of SER. The drug was exposed to alkaline, acidic, oxidative and photolytic degradation according to ICH guidelines. Moreover, the method was utilized to investigate the kinetics of oxidative degradation of the drug. The apparent first order rate constant and t 1/2 of the degradation reaction were determined.