Use of the Charge Transfer Reactions for the Spectrophotometric Determination of Risperidone in Pure and in Dosage Forms

The aim of study was to develop and validate two simple, sensitive, and extraction-free spectrophotometric methods for the estimation of risperidone in both pure and pharmaceutical preparations. They are based on the charge transfer complexation reactions between risperidone (RSP) as n-electron donor and p-chloranilic acid (p-CA) in method A and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) in method B as π-acceptors. In method A, RSP reacts with p-CA in methanol to produce a bright pink-colored chromogen measured at 530？nm whereas, in method B, RSP reacts with DDQ in dichloromethane to form orange-colored complex with a maximum absorption at 460？nm. Beer's law was obeyed in the concentration range of 0–25 and 0–50？μg/mL with molar absorptivity of and L/moL/cm for RSP in methods A and B, respectively. The effects of variables such as reagents, time, and stability of the charge transfer complexes were investigated to optimize the procedures. The proposed methods have been successfully applied to the determination of RSP in pharmaceutical formulations. Results indicate that the methods are accurate, precise, and reproducible (relative standard deviation %). 1. Introduction Risperidone(RSP)chemicallyknownas4-[2-[4-(6-fluorobenzo[d]isoxazole-3-yl)-1-piperidyl]ethyl]-3-methyl-2,6-diazabicyclo[4.4.0]deca-1,3-dien-5-one？？(Figure？？1), is the atypical antipsychotic drug with a relatively low incidence of extra pyramidal side effects. It is used for the treatment of schizophrenia, bipolar disorder, and behavior problems in people with autism. In 2003, the FDA-approved RSP for the short-term treatment of the mixed and manic states associated with bipolar disorder. It is also approved for the treatment of irritability in children and adolescents with autism in 2006. The drug is officially included in 2005 European Pharmacopeia, and the official method of its determination is high-performance liquid chromatography [1]. Figure 1: Structure of risperidone. Many methods have been employed for the determination of RSP in biological samples including HPLC with electrochemical detection [2, 3] and RP-HPLC with UV detection [4]. The most extensively used technique for its determination is LC-MS/MS, but several procedures using this technique are confined to biological fluids like human plasma [5–8], plasma and urine [9], and serum [10]. A limited number of analytical methods for the quantitative estimation of RSP in pharmaceutical samples are known. Procedures based on high-performance liquid chromatography and thin-layer densitometric methods [11], spectrophotometry