Background: Sertraline is an antidepressant drug from the family of selective serotonin reuptake inhibitors (SSRIs) and is used in the treatment of depression. Aim: The aim of this work was to develop a sensitive, precise, accurate, and specific analytical method for quantitative estimation of sertraline in pharmaceutical product for the purpose of using it as a quality control tool for testing sertraline products pre and post-market distribution, ensuring the presence of claimed drug amount in the pharmaceutical dosage form. Methods: Sertraline estimation in commercial drug products administered in hospitals and community drugstores and prescribed to patients through the development of an in-house High-Performance Liquid Chromatographic (HPLC) method to contribute with a validated, specific and sensitive method to literature methodologies. Results: The method is sensitive, specific, and selective, and showed linearity R2>0.999 within concentration range of 2.5 to 100 µg/mL for dissolution medium USP (pH 4.5), pH1.2, and 6.8. Accuracy results within the range of 98% - 102%, precision CV% less than 2%. The assayed tablets mean recovery is 100.676%. Moreover, the dissolution results meet the required 80 percent dissolution limit within 30 minutes for the USP dissolution medium (pH 4.5). Conclusion: The analytical method developed is very sensitive and totally validated for use in the quantitative analysis of sertraline.