QUALITY BY DESIGN (QBD) BASED APPROCH TO ANALYTICAL VALIDATION RP-HPLC METHOD DEVELOPMENT AND VALIDATION OF AMISULPRIDE IN BULK AND TABLETS

Sayali Rajendra Khadake*

ABSTRACT

Amisulpride is a second-generation (atypical) antipsychotic belonging to the substituted benzamide class. It exhibits selective dopamine D2 and D3 receptor antagonism, distinguishing it from many other atypical antipsychotics that also target serotonin receptors. Pharmacological profile: At low doses (50–300 mg/day): Blocks presynaptic D2/D3 autoreceptors, enhancing dopamine transmission—useful for negative symptoms (e.g., apathy, social withdrawal). At high doses (400–800+ mg/day): Blocks postsynaptic D2/D3 receptors, reducing positive symptoms (e.g., hallucinations, delusions). Therapeutic Uses: (1) Schizophrenia: Approved for the treatment of both positive and negative symptoms, Especially beneficial in patients who show primary negative symptoms or are sensitive to sedation and weight gain caused by other antipsychotics. (2) Dysthymia and Bipolar Depression (off-label in some countries): Low-dose amisulpride has shown antidepressant effects. (3) Nausea and Vomiting: Low-dose IV amisulpride (Barhemsys®) is FDA-approved for postoperative nausea and vomiting (PONV). (4) Functional Gastrointestinal Disorders (investigational): Being explored for functional dyspepsia and gastroparesis due to its gastroprokinetic properties. Advantages: Lower risk of metabolic side effects (e.g., weight gain, diabetes), Minimal sedation, Good efficacy for both acute and maintenance treatment. Limitations: Risk of hyperprolactinemia, especially at higher doses, QT prolongation potential—caution in cardiac-compromised patients, Not approved in the U.S. for psychiatric use (available in Europe, Asia, etc.). Aim of the study: The primary aim of this study is to develop and validate a robust, precise, and accurate Reverse Phase High-Performance Liquid Chromatography (RP-HPLC) method for the quantitative analysis of Amisulpride in bulk and tablet dosage forms, employing the Quality by Design (QbD) approach. This methodology integrates systematic experimental design and risk assessment tools to identify and control critical method variables, thereby ensuring method robustness, reliability, and regulatory compliance in accordance with ICH Q2(R1) guidelines.

Keywords: Amisulpride, Validation, RP- HPLC, Optimization, QBD.