Stress Degradation Studies on Flupirtine Maleate Using Stability-Indicating RP-HPLC Method

With the objective of developing an advanced method for rapid separation with shorter runtime, a simple, precise, and accurate stability-indicating isocratic RP-LC method coupled with PDA detector was developed for the quantitative determination of flupirtine maleate in bulk and in capsule dosage form. Good resolution between the peaks for degradation products and the analyte was achieved on a Waters Agilent XDB C18 ( ？mm, 5？μm) column using mobile phase containing a mixture of phosphate buffer pH 3.36 and acetonitrile in the ratio of 65？:？35. The eluted compounds were monitored at 344？nm and the flow rate employed for the present investigation was 1？mL/min. The newly developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision, and robustness. The method may be employed for the assay determination of flupirtine maleate in pharmaceutical dosage forms. 1. Introduction Flupirtine maleate is a nonopioid centrally acting, structurally dissimilar from other analgesics. It is amino pyridine derivative [1] with the chemical name ethyl 2-amino-6-(4-flurobenzylamino) 3-pyridyl carbamate maleate (Figure 1). The spectrum of action of flupirtine includes analgesia, muscle relaxation, and neuroprotection. The analgesic effect of flupirtine does not appear to be associated with any central opioid effect. Flupirtine does not appear to act on the usual binding sites of the N-methyl-D-aspartate receptor (NMDA) such as glycine site or polyamine site or the magnesium site. There is evidence to show that flupirtine may suppress the opening of the NMDA channel by acting as an oxidizing agent at the redox site of the NMDA receptor. Jakob and Krieglstein found an activation of G protein-regulated inwardly rectifying K+ channels (GIRKs) by flupirtine in therapeutically relevant concentration ranges [2]. The opening of these channels inhibits exaggerated neuronal action potential generation and controls neuronal excitability [3]. Figure 1: Structure of flupirtine maleate. Flupirtine is used for the treatment of acute and chronic pain, that is, for painful increased muscle tone of the posture and motor muscles, primary headache, tumor pain, dysmenorrhea, and pain after orthopedic operations and injuries. Some neuroprotective effects due to NMDA receptor antagonistic properties of flupirtine may also be used in the treatment of Creutzfeldt-Jakob disease, Alzheimer’s disease, and multiple sclerosis [4]. Stability testing forms an important part of the process of drug product