Validation of RP-HPLC Method and Stress Degradation for the Combination of Metformin HCl, Atorvastatin Calcium and Glimepiride: Application to Nanoparticles

Abstract

A stability-indicating high-performance liquid chromatography (HPLC) procedure was developed for the determination of metformin HCl (MTH), atorvastatin calcium (AC) and glimepiride (GP) in combination and their main degradation products. The separation and quantization were achieved on a 5-µm Qualisil gold, C18 column (4.6 mm × 250 mm). The mobile phase selected was phosphate buffer ( pH 2.9)-organic phase in proportion of 70:30. Organic phase consisted of methanol-acetonitrile (90:10) at a flow rate of 1 mL/min and detection of analytes was carried out at 230 nm. The method exhibited good linearity over the range of 10-60 µg/mL for MTH, 2-20 µg/mL for AC and 5-30 µg/mL for GP. Square of the correlation coefficients was found to be >0.999. Various stress degradation studies were carried out in combination as per International Conference of Harmonization (ICH) guidelines for 4 h. The recovery and precision were determined in terms of intraday and interday precisions and expressed as relative standard deviations. These were <1 and <2%, respectively. Finally, the applicability of the method was evaluated in nanoparticle analysis of MTH, AC and GP as well as in stability studies of nanoformulation.

Development and Validation of a Discriminating Dissolution Method for Atorvastatin Delayed-Release Nanoparticles Using a Flow-Through Cell: A Comparative Study Using USP Apparatus 4 and 1

“…The HPLC method used for the analysis of the aliquots was validated for various parameters to ensure suitability for estimating the release profile of the drug from ACDR NPs (12). …”

Forced Degradation Study of Statins: A Review

“…The degradation study of atorvastatin (ATV) was investigated by some researchers with a various method such as liquid chromatography-mass spectroscopy (LC-MS) [16], ultra performance liquid chromatography (UPLC) [17][18][19], and highperformance liquid chromatography (HPLC) [20][21][22][23][24]. Lakka et al conducted stress tests on ATV with HPLC method.…”

Determination of Chemical Stability of Two Oral Antidiabetics, Metformin and Repaglinide in the Solid State and Solutions Using LC-UV, LC-MS, and FT-IR Methods

“…According to some reports from the literature, metformin occurred similarly labile in acidic and alkaline media with the degradation of 5.97-7.73% and 4.66-6.47%, respectively [8,12]. On the other hand, the different results were also reported, according to which the degradation of the drug was significantly higher in alkaline (36.70-42.72%) than in acidic (0.5-15.24%) conditions [9,13]. Similarly, our study showed much higher degradation in 0.1 M NaOH than in 0.1 M HCl, i.e., 60.92 versus 5.63%.…”

“…Several stability-indicating HPLC and UHPLC methods were reported for the determination of metformin, mainly in combination with other antidiabetic drugs, like sitagliptin, linagliptin, alogliptin, vildagliptin, dapagliflozin, empagliflozin, pioglitazone, and glimepiride [7][8][9][10][11][12][13][14][15][16][17][18]. Additionally, stability-indicating HPTLC methods have been reported for similar purposes [19,20].…”