The development and validation of analytical methods for the quantitative determination of dabigatran etexilate by HPLC-DAD and UV spectrophotometry during a comparative dissolution kinetics test of dabigatran capsules in the biorelevant FaSSGF medium

Introduction. Venous thromboembolism and atrial fibrillation are significant causes of vascular mortality. Anticoagulant therapy significantly reduces the risk of ischemic stroke, and dabigatran etexilate, a direct thrombin inhibitor, has become firmly established in clinical practice. There are several generic drug products of dabigatran etexilate capsules in Russia. Comparative dissolution kinetics test (CDKT) is one of the most critical quality control method for this dosage form. The use of biorelevant dissolution media can reliably predict the in vivo dissolution of the capsules. Based on the pharmacokinetic properties of dabigatran etexilate capsules, the most suitable medium is Fasted State Simulated Gastric Fluid (FaSSGF).

Aim. Development and validation of analytical methods for the quantitative determination of dabigatran etexilate using high performance liquid chromatography with diode array detection (HPLC-DAD) and UV spectrophotometry during the CDKT of dabigatran etexilate capsules in the biorelevant dissolution medium FaSSGF.

Materials and methods. Model solutions containing dabigatran etexilate pellets and excipients of the drug product were analyzed. An Agilent 1260 Infinity II Series HPLC-DAD (USA) was used for chromatographic separation. Detection of dabigatran was performed at 316 nm wavelength. A ZORBAX SB-C18, 150 × 4.6 mm, 5 µm column with ZORBAX SB-C18, 12.5 × 4.6 mm, 5 µm guard column (Agilent Technologies, USA) were used. An SF-2000 spectrophotometer (Russia) was used for the development and validation of UV spectrophotometry analytical method. Data obtained was processed using Agilent OpenLab CDS v. 2.7 and OKB Spectr Scanning for spectrophotometer SF-2000 v. 4.06.

Results and discussion. Optimal conditions for sample preparation, chromatographic and spectrophotometric conditions were developed for the quantitative assessment of dabigatran etexilate released into the FaSSGF dissolution medium during CDKT. Developed analytical methods were validated in the range from 0.13 to 14.67 μg/ml.

Conclusion. Developed analytical methods provide reproducible and reliable results over the entire specified range thus are suitable for the quantitative determination of dabigatran etexilate during CDKT in the biorelevant FaSSGF dissolution medium.

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