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Thursday, 8 November 2018

Development and Validation of Zero and First-Order Derivative Area under Curve Spectrophotometric Methods for the Determination of Midodrine Hydrochloride in Bulk Material and in Pharmaceutical Dosage Form






Hydrochlorideis a long acting α-adrenergic agonist that causes elevation of systemic blood pressure, accompanied by a reduction in heart rate. Midodrine is a pro-drug of desglymidodrine (DMAE), developed by the attachment of the amino acid approach glycine to the functional amine of DMAE. It is therapeutically used, as a racemic (rac) mixture, for the treatment of orthostatic hypotension. The pro-drug Midodrine is primarily converted into its active metabolite desglymidodrine after oral administration, mainly in the liver and in the systemic circulation by unknown peptidases. After oral administration, Midodrine is rapidly absorbed. The plasma levels of the pro-drug peak after about half an hour, and decline with a half- life of approximately 25 minutes, while the metabolite reaches peak blood concentrations about 1 to 2 hours after a dose of Midodrine and has a half-life of about 3 to 4 hours. Until now, the metabolism of Midodrine has not been extensively studied. Midodrine was developed by an amino-acid approach through the glycine promoiety attachment to the functional amine of desglymidodrine. Midodrine is a substrate for the intestinal H+ -coupled peptide transporter 1 (hPEPT1). This carrier mediated transport raises the bioavailability of Midodrine Hydrochloride to 93% when compared with 50% for desglymidodrine.

Asuitable and validated method should be vacant for the drug delivery system for analysis of bulk drug, for release dissolution studies and estimation of drug in biological samples. The literature survey acknowledges that various methods for the determination of Midodrine hydrochlorides are noted. Some methods have been developed based on radioisotope-labeled techniques, High Performance Liquid Chromatography (HPLC) with fluorescence and Ultraviolet (UV) detection, and the Capillary Electrophoresis (CE). Hence, our study reports a simple, precise and economical UV- Spectrophotometric method for estimation of Midodrine Hydrochloride in bulk and tablet formulation. The method was validated according to ICH guidelines.

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