Stability Indicating HPLC Determination of Risperidone in Bulk Drug and Pharmaceutical Formulations

The objective of the current study was to develop a validated stability-indicating assay method (SIAM) for risperidone after subjecting it to forced decomposition under hydrolysis, oxidation, photolysis, and thermal stress conditions. The liquid chromatographic separation was achieved isocratically on a symmetry C18 column (5？μm size, 250？mm × 4.6？mm i.d.) using a mobile phase containing methanol: acetonitrile (80？:？20, v/v) at a flow rate of 1？mL/min and UV detection at 280？nm. Retention time of risperidone was found to be . The method was linear over the concentration range of 10–60？μg/mL with a limit of detection and quantitation of 1.79 and 5.44？μg/mL, respectively. The method has the requisite accuracy, specificity, sensitivity, and precision to assay risperidone in bulk form and pharmaceutical dosage forms. Degradation products resulting from the stress studies did not interfere with the detection of Risperidone, and the assay is thus stability indicating. 1. Introduction Risperidone, 4-[2-[4-(6-fluorobenzo[d]isoxazol-3-yl)-1-piperidyl] ethyl]-3-methyl-2,6-diazabicyclo[4.4.0]deca-1,3-dien-5-one an atypical antipsychotic drug used for the treatment of schizophrenia, the mixed and manic states associated with bipolar disorder, and irritability in children with autism [1]. Blockade of dopaminergic D2 receptors in the limbic system alleviates positive symptoms of schizophrenia such as hallucinations, delusions, and erratic behavior and speech. Blockade of serotonergic 5-HT2 receptors in the mesocortical tract causes an excess of dopamine, resulting in an increase in dopamine transmission and an elimination of core negative symptoms. It has high affinity for D2 dopaminergic receptors. It has actions at several 5-HT (serotonin) receptor subtypes. These are , linked to weight gain, , linked to its antipsychotic action and relief of some of the extrapyramidal side effects experienced with the typical neuroleptics through action at . Like other 5-HT2 antagonists, risperidone also binds at alpha (1)-adrenergic receptors and, to a lesser extent, at histamine H1 and alpha (2)-adrenergic receptors [2]. Several analytical methods have been reported in the literature for the analysis of Risperidone from pharmaceutical dosage form. The techniques include chemiluminescence [3], RP HPLC [4], TLC [5], and visible spectrophotometry [6] and so forth forms. There are numerous methods to quantify Risperidone in biological fluid and human plasma, including HPLC combined with capillary electrophoresis [7], HPLC-DAD [8], HPLC-MS/ MS [9], RP-HPLC [10], LC-MS/MS [11–13],