SIMULTANEOUS DETERMINATION OF METFORMIN, LINAGLIPTIN IN JENTADUETO AND METFORMIN, SAXAGLIPTIN IN KOMBIGLYZE BY LC-MS METHOD

P B.N Prasad,K Satyanarayana,G Krishna Mohan

doi:10.22159/ijpps.2018v10i3.23187

Abstract

Objective: The objective of the present investigation was to develop a novel, simple and economic method for the determination of metformin (MET), linagliptin (LIN) and saxagliptin (SAX) in jentadueto and kombiglyze sample by employing the liquid chromatography and mass spectrometric method for estimation in bulk and pharmaceutical dosage form in presence of degradation products.Methods: The chromatographic separation was achieved by using the mobile phase composition of methanol and ammonium acetate buffer pH 4.5 (85:15 % v/v) on the Hypurity advance C-18 column at a flow rate of 0.5 ml/min. Ion signals m/z “130.10/70.10, 473.10/420.40 and 316.30/180.20” for metformin, linagliptin and saxagliptin respectively measured in positive ion mode. The detailed validation of the method was performed as per ICH guidelines.Results: The results of all validation parameters found within acceptance limits. The linearity of the drugs was found to be in the concentration range of 50–5000 ng/ml for all the drugs. Accuracy of the drugs was found to be from 94-102% and precision was found 4.67% RSD for all three drugs. The validated method was employed for the determination of drugs in the formulation and also determined the drugs in the presence of degradation products under stress conditions.Conclusion: The method was developed and validated as per guidelines. Hence, this method can be used for the simultaneous determination of metformin, linagliptin and metformin, saxagliptin in bulk and combined dosage forms.

Highlights

Biguanide class drug metformin hydrochloride (N,N-dimethyl imido carbonamide diamide), an oral anti-diabetic drug is used as a firstline choice for the treatment of type 2 diabetes, in overweight or obese people and those with normal kidney function
Saxagliptin is a potent, selective, reversible dipeptidyl peptidase 4 (DPP4) inhibitor designed for extended inhibition of the DPP4 enzyme
Metformin hydrochloride (MET, 99.35%), linagliptin (LIN, 98.26%) and saxagliptin (SAX, 99.59%) are from Clearsynth Company, Mumbai, India. ammonium acetate, formic acid and methanol are purchased from Merck Ltd, Mumbai, India

Summary

Introduction

Biguanide class drug metformin hydrochloride (N,N-dimethyl imido carbonamide diamide), an oral anti-diabetic drug is used as a firstline choice for the treatment of type 2 diabetes, in overweight or obese people and those with normal kidney function. Linagliptin, 8-[(3R)-3-aminopiperidin-1-yl]-7-(but-2-yn-1-yl)-3-methyl1-[(4-ethylquinazolin-2-yl) methyl]-3,7-dihydro-1H-purine-2,6dione] is a novel dipeptidyl peptidase-4 inhibitor representing a new therapeutic approach by stimulating glucose-dependent insulin release and reduction of glucagon levels. It acts through inhibiting the inactivation of incretins glucagon-like peptide-1 and gastric inhibitory polypeptide [4, 5]. DPP-4 inhibitors represent a new therapeutic approach to the treatment of type-II diabetes that functions to stimulate glucose-dependent insulin release and reduce glucagon levels. This is done through inhibition of incretins inactivation, glucagon-like peptide-1 and gastric inhibitory polypeptide, thereby improving glycemic control [7]

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Discussion

Conclusion