Quantitative Determination and Validation of Metformin Hydrochloride in Pharmaceutical Using Quantitative Nuclear Magnetic Resonance Spectroscopy

Abstract

Rapid, specific and accurate proton nuclear magnetic resonance spectroscopy (1H NMR) method was developed to determine metformin hydrochloride antidiabetic drug in pharmaceutical tablet formulation. The method was based on quantitative NMR spectroscopy (qNMR) using maleic acid as an internal standard and deuterium oxide (D2O) as a diluent. For the quantification of the drug, the (1H NMR signals at 2.91 ppm and 6.25 ppm corresponding to the analyte proton of metformin hydrochloride and maleic acid internal reference standard (IS) respectively were used. The method was validated for the parameters of specificity and selectivity, precision and intermediate precision, linearity, range, limit of detection (LOD) and limit of quantification (LOQ), accuracy, solution stability and robustness. The linearity of the calibration curve for analyte in the desired concentration range was good (R2=0.9993). The method was accurate and precise with good recoveries. Range study was also performed up to saturation level (152.67 mg/0.60 mL) in D2O. The advantage of the method is that no reference standard of analyte drug is required for quantification. The method is nondestructive and can be applied for quantification of metformin hydrochloride in commercial formulation products.

Counterion Affects Interaction with Interfaces: The Antidiabetic Drugs Metformin and Decavanadate

“…[43] In D 2 O and [D 4 ]MeOH, the NH protons exchange, and only one peak at δ = 2.91 (D 2 O) or 3.03 ppm (MeOH) of the CH 3 group is observed. [44] Integration of CH 3 , NH 2 , and NH 2 + signals give the ratio 3:2:1, respectively, and are consistent with the previous report.…”

A simple and accurate protocol for absolute polar metabolite quantification in cell cultures using quantitative nuclear magnetic resonance

“…PULCON standard reference signal for calibration was provided by a freshly prepared 10-mM DMS solution. Before each series of acquisitions, a system suitability test [23] was performed on the calibration solution to assess specificity and sensitivity of the spectrometer. Acceptance criteria were the following: line width at half-height of a singlet DMS signal <1.5 Hz, percentage relative standard deviation (STD %) 4 in the dynamic range of 10 3 , and difference in chemical shift <0.2 Hz.…”

“…The LOD and LOQ can be calculated by the standard deviation of the response s and the slope S of the linear regression using the lowest values of concentration, close to zero, assuming as confidence levels 3.3s for the LOD and 10s for the LOQ, as described by the following formula [23]: LOD ¼ 3:3s=S and LOQ ¼ 10s=S; (1) where s is the standard deviation of the response (i.e., the square root of the sum of the squared distance of each measurement point from the linear regression line, divided for n À 1 points, used for linear regression fitting) and S is the slope of the regression line. The (not mediated) data obtained from the concentration range 5e70 mM, previously exploited for the linearity test, were subjected to a new least-squares linear regression.…”

Determination of metformin at metal-organic framework (Cu-BTC) nanocrystals/multi-walled carbon nanotubes modified glassy carbon electrode

“…1 Developing sensitive, simple and fast methods for measurement of metformin in biological samples is needed for pharmacokinetic and pharmacological studies. Several methods have been proposed for its quantitative analysis including capillary electrophoresis, 2,3 chromatography, 4 -13 NMR spectrometry, 14 spectrophotometry, 15 -24 conductometry 25 and IR spectrometry. 26 However, some of these methods suffer from disadvantages such as long analysis time, complicated sample preparation procedures, and very costly instrumentation.…”