Note

Separation and determination of sertraline and its metabolite, desmethylsertraline, in mouse cerebral cortex by reversed-phase high-performance liquid chromatography

In this study, a screening on reversed-phase stationary phases (including C₈, C₁₈, CN, PEG and amide) was carried out in order to obtain an efficient HPLC method for the determination of sertraline and three of its more closely related synthetical and non-chiral impurities, without using ion-pair reagents. The best results in terms of both retention time and resolution of the target analytes were obtained with a Zorbax Bonus-RP column, which contains a polar amide group embedded in a C₁₄ alkyl chain.

Once the most suitable stationary phase was chosen, the HPLC method was optimized by using a factorial design, evaluating three quantitative factors (column temperature, buffer pH and buffer concentration) in order to find the best conditions which maximize the resolution between impurities A and B (positional isomers) and minimize the total run time. The final HPLC conditions were set by means of a second experimental design, which allowed optimizing the effects of the buffer pH and the proportion of methanol in the mobile phase.

The optimal conditions for simultaneously determining sertraline and its impurities, being baseline separated in less than 10 min, were finally obtained with Zorbax Bonus-RP column (150 mm × 4.6 mm, 5 μm), under isocratic conditions with phosphate buffer (pH 2.8; 10 mM)–methanol (63:37, v/v) at 50 °C, at the flow-rate of 1.0 mL/min. UV detection was set at 220 nm.

This method was successfully validated following ICH guidelines and it proved to be reliable for the determination of sertraline and related impurities in tablets as pharmaceutical forms.

A precise, sensitive and high throughput liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for simultaneous determination of sertraline (SER) and its primary metabolite, N-desmethyl sertraline (NDS) in human plasma is developed and validated. The analytes and the internal standard-fluoxetine were extracted from 300 μL aliquots of human plasma via liquid–liquid extraction in methyl tert-butyl ether. Chromatographic separation was achieved in a run time of 2.5 min on a Betasil C8 column (100 mm × 2.1 mm, 5 μm) under isocratic conditions. Detection of analytes and IS was done by tandem mass spectrometry, operating in positive ion and multiple reaction monitoring (MRM) acquisition mode. The protonated precursor to product ion transitions monitored for SER, NDS and IS were m/z 306.2 → 159.0, 292.1 → 159.0 and 310.6 → 148.4, respectively. The method was fully validated for its sensitivity, selectivity, linearity, accuracy and precision, matrix effect, stability study and dilution integrity. A linear dynamic range of 0.5–150 ng/mL was established for both the analytes with mean correlation coefficient (r) of 0.9993 and 0.9980, respectively. The intra-batch and inter-batch precision (%CV) across five quality control levels was ≤10.4% for both the analytes. The method was successfully applied to a bioequivalence study of 100 mg sertraline tablet formulation in 32 healthy Indian male subjects under fasting condition.

Sertraline is a widely used antidepressant belonging to the selective serotonin reuptake inhibitor class; its efficacy has been demonstrated not only in the treatment of major depression, obsessive compulsive and panic disorders, but also for eating, premenstrual dysphoric and post-traumatic stress disorders.

Several methods have been published for the determination of sertraline in pharmaceuticals, biological materials and environmental samples. The purpose of the current review is to provide a systematic survey of the latest analytical techniques for the determination of sertraline covering the period from 1987 until 2008.

The applicability of hollow fiber-based liquid phase microextraction (HF-LPME) was evaluated for the extraction and preconcentration of three antidepressant drugs (amitriptyline, imipramine and sertraline) prior to their determination by HPLC-UV. The target drugs were extracted from 11.0 mL of aqueous solution with pH 12.0 (source phase) into an organic extracting solvent (n-dodecane) impregnated in the pores of a hollow fiber and finally back extracted into 24 μL of aqueous solution located inside the lumen of the hollow fiber and adjusted to pH 2.1 using 0.1 M of H₃PO₄ (receiving phase). The extraction was performed due to pH gradient between the inside and outside of the hollow fiber membrane. In order to obtain high extraction efficiency, the parameters affecting the HF-LPME including pH of the source and receiving phases, the type of organic phase, ionic strength and volume of the source phase, stirring rate and extraction time were studied and optimized. Under the optimized conditions, enrichment factors up to 300 were achieved and the relative standard deviation (R.S.D.%) of the method was in the range of 2–12%. The calibration curves were obtained in the range of 5–500 μg L⁻¹ with reasonable linearity (R² > 0.998) and the limits of detection (LODs) ranged between 0.5 and 0.7 μg L⁻¹ (based on S/N = 3). Finally, the applicability of the proposed method was evaluated by extraction and determination of the drugs in urine, plasma and tap water samples. The results indicated that hollow fiber microextraction method has excellent clean-up and high-preconcentration factor and can be served as a simple and sensitive method for monitoring of antidepressant drugs in the biological samples.

A liquid chromatographic method with ultraviolet detection was developed for the analysis of the recent antidepressant sertraline and its main metabolite N-desmethylsertraline in human plasma. The analytes were separated on a C8 reversed phase column, using a mobile phase composed of acetonitrile and a 12.3 mM, pH 3.0 phosphate buffer containing 0.1% triethylamine (35:65, v/v). Clomipramine was used as the Internal Standard. Using a solid phase extraction procedure with C2 cartridges high extraction yields (>94%) and good purification from matrix interference were obtained. Good linearity was obtained in the 7.5–250.0 ng mL⁻¹ range for sertraline and in the 10–500 ng mL⁻¹ range for N-desmethylsertraline. The analytical method was validated in terms of precision, extraction yield and accuracy. These assays gave R.S.D.% values for precision always lower than 3.9% and mean accuracy higher than 90%. Thanks to its good selectivity, the method proved to be suitable for the analysis of plasma samples from patients treated with sertraline as either monotherapy or polypharmacy.

A method for the determination of sertraline, a new antidepressant drug and a selective serotonin reuptake inhibitor (SSRI), in human plasma is described. Therapeutic drug monitoring (TDM) necessitates efficient, fast and reliable analytical methods validated by external quality control. We therefore devised a simple, rapid and sensitive isocratic reversed-phase liquid chromatographic-tandem mass spectrometric method equipped with Turbo Ion spray (TIS) source, operating in the positive ion and selective reaction monitoring (SRM) acquisition mode to quantify sertraline in human plasma. A new and superior procedure of solid-phase extraction (SPE) (compared to liquid–liquid extraction) was followed to extract sertraline and imipramine as internal standard (IS) from the human plasma. Sample preparation was performed using waters hydrophilic–lipophilic balance (HLB) cartridge and this method yielded extremely clean extracts with very good recovery, 81.47 and 85.79% for sertraline and IS, respectively. Both were analyzed by combined reverse phase liquid chromatography and tandem mass spectrometry (LC–MS/MS) with positive ion TIS ionization using SRM acquisition mode. The response of the LC–MS/MS method for sertraline was linear over the dynamic range of 0.5–60.0 ng/ml with correlation coefficient r ≥ 0.9996. The coefficient of variance (%CV) was 8.53% at 0.5 ng/ml and the accuracy was well within the accepted limit of ±20% at lower limit of quantification (LLOQ) and ±15% at all the other concentrations in the linear range. This method was fully validated for the accuracy, precision and stability studies. The above findings indicate that the method is very much accurate and precise and can be successfully applied for bioequivalence studies in human subjects.