Stability-indicating Capillary Electrophoresis Method Research Articles

Stability-indicating capillary electrophoresis method for the simultaneous determination of metformin hydrochloride, saxagliptin hydrochloride, and dapagliflozin in pharmaceutical tablets

A capillary electrophoretic method coupled to a diode array detector (CE-DAD) was developed and validated for the simultaneous determination of metformin hydrochloride (MET), the dipeptidyl peptidase-4 (DPP-4) inhibitor saxagliptin hydrochloride (SAX), and the sodium glucose co-transporter (SGLT 2) inhibitor dapagliflozin (DAP). The proposed method was used for the determination of these drugs in binary antidiabetic combinations namely, SAX/MET, combination I, DAP/MET, combination II, and SAX/DAP, combination III. CE separation was performed on a fused silica capillary with background electrolyte consisting of 30 mM phosphate buffer (pH 6.0) with a high voltage of 30 kV, a pressure of 20 mbar, and an injection time of 40 s. The compounds were detected at 203 nm for SAX/DAP and 250 nm for MET. The method was linear in the concentration range of 10–200 µ g/mL (SAX), 1.25–50 µ g/mL (DAP), and 7.5–1000 µ g/mL (MET). Full validation of the proposed method was performed as per the ICH guidelines. The obtained errors and deviation values did not exceed 2% assessing good accuracy and precision, respectively. The stability-indicating potential of the proposed method was proved under different stress-degradation conditions. The proposed method was successfully applied to the analysis of the three binary combinations in their tablets.

A stability-indicating capillary electrophoresis method for the determination of emtricitabine and tenofovir disoproxil fumarate in pharmaceutical tablets

A stability-indicating capillary electrophoresis method coupled to a diode array detector (DAD) was developed and validated for the simultaneous determination of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) in combined tablets. This proposed method utilized a fused silica capillary (effective length, 62 cm; internal diameter [ID], 75 μm) and a background electrolyte (BGE) consisting of phosphate solution (pH 9.5, 50 mM). The separation was achieved at a voltage of 25 kV and a temperature of 21 °C using paracetamol as an internal standard. The described method was linear over the range of 5–200 μg/mL for both drugs (r = 0.9992). Intra- and inter-day relative standard deviation (RSD) (n = 9) was 0.41%. The limits of detection for FTC and TDF were 1.25 and 1.00 μg/mL, respectively. The average percentage recoveries of FTC and TDF from their tablet formulations were 99.66 ± 0.73 and 99.48 ± 0.33, respectively. The two drugs were subjected to thermal, photolytic, hydrolytic, and oxidative stress conditions, and then the stressed samples were analyzed by the proposed method. Degradation products produced as a result of stress studies did not interfere with the detection of FTC and TDF. The assay can thus be considered stability indicating.

Development and Validation of a Stability-Indicating Capillary Electrophoresis Method for the Determination of Zolpidem Tartrate in Tablet Dosage Form with Positive Confirmation using 2D- and 3D-DAD Fingerprints.

The aim of the current study was to develop a simple, precise, and accurate capillary zone electrophoresis method for the determination of zolpidem tartrate in tablet dosage form. Separation was conducted in normal polarity mode at 25°C, 22 kV, using hydrodynamic injection for 10 s. Separation was achieved using a background electrolyte of 20 mM disodium hydrogen phosphate adjusted with phosphoric acid (85%), pH at 5.50, and detection at 254 nm. Using the above optimized conditions, complete determination took place in less than 3 min using amiloride HCl as the internal standard. The method was linear over the range of 3–1000 μg mL−1 with a correlation coefficient of 0.9999. Forced degradation studies were conducted by introducing a sample of zolpidem tartrate standard and pharmaceutical sample solutions to different forced degradation conditions, being neutral (water), basic (0.1 M NaOH), acidic (0.1 M HCl), oxidative (10% H2O2), temperature (60°C in oven for 3 days), and photolytic (exposure to UV light at 254 nm for 2 h). Degradation products resulting from the stress studies did not interfere with the detection of zolpidem tartrate and the assay can be considered stability-indicating.

DETERMINATION OF CINACALCET HYDROCHLORIDE BY CAPILLARY ELECTROPHORESIS WITH PHOTODIODE ARRAY DETECTION

This article reports a validated stability-indicating capillary electrophoresis method using a photodiode array detector at 220 nm for the determination of cinacalcet hydrochloride. The best electrophoretic separation between the analyte and internal standard (lamotrigine) was achieved within 5 min in a deactivated fused silica capillary (55 cm effective length × 75 µm internal diameter) maintained at 24°C using a background electrolyte solution consisted of phosphate buffer (50 mM, pH 6.4):methanol (95:5, v/v) at a separation voltage of 30 kV. The linear range of the method was 0.5–30 µg/mL (r = 0.9999) with limits of detection and quantitation of 0.1 and 0.5 µg/mL, respectively. The assay precision and accuracy were favorable as the relative standard deviations did not exceed 1.09%, and the recovery values were 98.99–100.33 ± 0.19–1.09%. The induced degradation products, when any, did not interfere with the detection of analyte. The proposed method was successfully applied for the determination of cinacalcet hydrochloride in bulk and pharmaceutical formulations; the percentage recovery values were 98.16–102.00 ± 0.24–1.08%. The results demonstrated the value of the method.

Validated Stability-Indicating Capillary Electrophoresis Method for the Separation and Determination of a Fixed-Dose Combination of Carvedilol and Hydrochlorothiazide in Tablets

A novel, fast, sensitive, and specific capillary electrophoresis (CE) technique coupled to a diode array detector has been developed for the separation and simultaneous determination of carvedilol (CRV) and hydrochlorothiazide (HCT) in two combination formulations. The proposed method utilized a fused silica capillary (55 cm x75 microm id) and the background electrolyte solution phosphate buffer (12.5 mM, pH 7.4)-methanol (95+5, v/v). The separation was achieved at 30 kV applied voltage and 24 degree C. Atorvastatin (80 microg/mL) was chosen as the internal standard. The described method was linear over the range of 1-200 and 0.2-150 microg/mL for CRV and HCT, respectively. Intraday and interday RSD (n = 6) was < or =1.4%. The LOD values of CRV and HCT were 0.26 and 0.07 microg/mL, respectively. The validated CE method was successfully applied to the analysis of two commercial tablet dosage forms. Forced degradation studies were performed on bulk samples of the two drugs using thermal, photolytic, hydrolytic, and oxidative stress conditions, and the stressed samples were analyzed by the proposed method. Degradation products produced as a result of stress studies did not interfere with the determination of CRV and HCT; the assay could, therefore, be considered stability-indicating.

DEVELOPMENT AND VALIDATION OF A STABILITY INDICATING CAPILLARY ELECTROPHORESIS METHOD FOR THE DETERMINATION OF RISEDRONATE IN TABLETS

A rapid, simple, and stability-indicating capillary electrophoresis method with UV detection was developed and validated for the assay of risedronate in tablet formulation. During our studies, the effects toward the crucial factors such as the buffer type, concentration and pH, applied voltage, and injection time were investigated. Optimal separation and determination was obtained utilizing 15 mM citric acid-disodium hydrogen phosphate (pH 6.0) as running buffer, applied voltage of 20 kV, and UV detection at 262 nm on an uncoated fused-silica capillary column. Under the optimal conditions, each electrophoretic run was completed within 5 min. The optimized method demonstrated good performance concerning selectivity, robustness, linearity (r 2 = 0.9997), sensitivity (limit of detection: 3 µg/mL), accuracy (95.32–97.43%) and precision (<2.26%). The stability indicating capability of the method was established by enforced degradation studies combined with peak purity assessment using calculated the response ratio of risedronate using peak areas integrated at both 210 and 262 nm. As a good alternative to the HPLC method, this approach has been successfully employed for the determination of the commercial available risedronate tablets.

Development of a stability-indicating capillary electrophoresis method for norfloxacin and its inactive decarboxylated degradant

A simple, accurate, precise, rapid and sensitive stability-indicating capillary electrophoresis (CE) method was optimized and validated for the simultaneous determination of norfloxacin and its inactive decarboxylated degradant in pharmaceuticals. The univariant method was used to optimize electrophoretic factors including injection time, separation voltage and column temperature. Electrolyte concentration and pH were optimized using the factorial design and response surface methods. The optimum conditions obtained were: 10 mmol l − 1 phosphate at pH 2.5, hydrodynamic injection time of 8 s at pressure 0.5 p.s.i., separation voltage 25 kV and column temperature 25 °C. The separation was carried out into a fused-silica capillary column (31.2 cm length × 50 μm i.d.) with detection at 301 and 285 nm for the intact drug and the degradant, respectively using a diode array detector. For both analytes, the method enjoys wide dynamic range (1–50 μg ml − 1 ) with good detectability (limits of detection 0.11 μg ml − 1 ). In addition, acceptable accuracy (recovery > 95%); and good repeatability and intermediate precision (RSD < 3.5%) were obtained.