Rp-HPLC and Chemometric Methods for the Determination of Two Anti-Diabetic Mixtures; Metformin Hydrochloride-Canagliflozin and Metformin Hydrochloride-Gliclazide in Their Pharmaceutical Formulation

Abstract

Objective: To develop and validate novel more sensitive analytical methods for the concurrent quantification of metformin-canagliflozin and metformin-gliclazide in their bulk forms and in their pharmaceutical preparations.
 Methods: Two methods were developed based on several chemometric assisted spectrophotometric methods and a Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC). The first method applies different spectrophotometric chemometric assisted methods, including ratio difference, derivative ratio and extended ratio subtraction method, while the second method describes a RP-HPLC separation of metformin hydrochloride-canagliflozin and metformin hydrochloride-gliclazide binary mixtures using a C18 column with a mobile phase consisting of acetonitrile: potassium dihydrogen phosphate (adjusted to pH 3) with sodium lauryl sulphate as additive in the ratio of 30:70 (%v/v) in isocratic elution mode at 1 ml/min.
 Results: The proposed methods were able to quantify each of the studied drugs in their binary mixtures with high percentage recoveries in both methods. The spectrophotometric methods were able to quantify each of metformin, canagliflozin and gliclazide in the ranges of 2.0-20.0 μg/ml, 1.5-40.0 μg/ml and 2.0-30.0 μg/ml, respectively. The RP-HPLC method produced well-resolved peaks at a retention time of 3.92, 6.92 and 9.10 min in the concentration ranges of 50.0-300.0 μg/ml, 5.0-50.0 μg/ml and 10.0-100.0 μg/ml for metformin, canagliflozin and gliclazide, respectively. The proposed methods were optimized and validated in accordance to the International Conference of Harmonisation (ICH) guidelines in terms of linearity, LOD, LOQ, precision and accuracy.
 Conclusion: The developed methods were found to be sensitive and reproducible methods for the simultaneous determination of anti-diabetic binary mixtures; metformin hydrochloride-canagliflozin and metformin hydrochloride-gliclazide. And thus were successfully employed for the quality control analysis of the pharmaceutical formulations of the studied binary mixtures.

A New Stability Indicating Uplc Method for the Determination of Two Antidiabetic Drugs in Combination: Applications to Bulk and Tablet Formulation

“…A thorough literature survey disclosed that several analytical and bioanalytical method development and validation reports were available for the assay of Metformin and Gliclazide simultaneously using ultraviolet (UV) spectrophotometry in bulk and formulations [14,15], High-Performance Liquid Chromatography (HPLC) in bulk and formulations [16][17][18][19][20][21], High-performance Thin-layer chromatography (HPTLC) in bulk and formulation [22], and HPLC in biological fluids [23]. However, there was no sufficient information reported elsewhere in the literature for the simultaneous determination of Metformin and Gliclazide in bulk and their fixeddose formulations using UPLC.…”

Ecofriendly appraisal of stability‐indicating high‐performance chromatographic assay of canagliflozin and metformin with their toxic impurities; in silico toxicity prediction

“…While MET along with its two impurities; CG (related compound A) [7] and ML (related compound D) [7] was determined by different methods [7,8,14,15]. Both CN and MT were determined together either in pharmaceutical formulations or biological fluids by different analytical methods as well [9,[16][17][18][19][20] also, an HPLC-diode array detection stability study for CN and MT determination in dosage forms was reported at which the forced degradation products were separated from both drugs without their quantification or chemical structure elucidation [21]. The literature survey showed no reported analytical method for the determination of CN, MT, their respective major degradation products DG and CG along with MT toxic impurity, ML.…”