Benzodiazepines (BZDs) are a group of drugs prescribed for their sedating effect. Their misuse and addictive properties stipulate different authorities for developing simple, fast and accurate analytical methods for instantaneous detection. Differential pulse voltammetric technique (DPV) was utilized for the selective assay of midazolam hydrochloride (MDZ) in the pure, parenteral dosage forms and plasma samples. A chemically modified carbon paste electrode (CPE) was implemented during the study. The method depended on the electroreduction of MDZ on the surface of the electrode over a potential range of 0.0 V to -1.6 V. The electrode was fabricated using silica nanoparticles (Si-NPs) which were incorporated into the composition of the CPE and used to enhance the electrode performance. Then, to enhance the sensitivity of the method, a chronoamperometric modification step was applied for depositing gold nanoparticles (Au-NPs) on the carbon paste electrode surface. Modification with Au-NPs showed a higher reduction current peak for MDZ with well-defined peaks. Various parameters such as pH of the media and measurements scan rate were investigated and optimized to enhance the sensor sensitivity. The sensor showed a dynamic linear response over a concentration range of 4.0 × 10-7 M to 2.9 × 10-4 M of MDZ with a LOD of 2.24 × 10-8 M using 0.1 M acetate buffer (pH 5.6). The sensor was validated in accordance with the ICH guidelines regarding accuracy, precision and specificity for the selective assay of MDZ in the presence of excipients. A greenness evaluation was performed using three different assessment tools, namely, the "Green Analytical Procedure Index" (GAPI), the "Analytical Greenness metric" (AGREE) and the "Whiteness Analytical Chemistry tool" (WAC) using the RGB12 model.
Keywords: Carbon paste electrode; Conscious sedating drug; Gold nanoparticles; Greenness metrics; Midazolam; Silica nanoparticles.
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