Development and Validation of the MEKC Method for a Stabilityindicating Assay of Midazolam in Pediatric Syrup

Abstract

The preparation of a parenteral solution for oral use leads the clinician to question the stability of drugs when used in conjunction with flavored oral suspending vehicles. Therefore, the purpose of this study was the evaluation of the stability of midazolam, frequently used as an oral premedication in children, in extemporaneously prepared pediatric syrup, using micellar electrokinetic capillary chromatography (MEKC). The optimization of parameters affecting electrophoretic separation provided adequate separation of the analyte of interest, the internal standard (nitrazepam) and the syrup ingredients in a short time of 8 min. As a separation buffer 10 mM sodium tetraborate, 30 mM SDS and 15% methanol were used. During the separation process analytes were detected at 254 nm. Suitable linearity ranged from 1 to 50 µg/ml (r= 0.998), sensitivity (limit of detection 0.12 µg/ml) and recovery (in the range of 100.1% for 50 μg/mL to 119.0% for 1 μg/mL) were achieved. In this experiment syrup samples were stored at different temperatures (4°C, 25°C and 40°C) in amber glass bottles to protect them from access to light. The analysis of properly prepared samples was carried out for 30 days, indicating the concentration of active substances and the pH of the syrup. Studies have confirmed that the most stable formulation was one stored in a refrigerator. The elaborated method can find reasonable application in the determination of midazolam in pharmaceutical formulations, as a stability-indicating assay. Keywords: Micellar electrokinetic chromatography (MEKC), midazolam, pediatric syrup, stability.