DEVELOPMENT AND VALIDATION OF A STABILITY INDICATING UPLC METHOD FOR THE ESTIMATION OF R-TELAPREVIR IN DRUG SUBSTANCE AND PHARMACEUTICAL DOSAGE FORM OF TELAPREVIR BY ENHANCED APPROACH
Keywords:
UPLC, Stability-indicating method, QbD with Design-of-Experiments approach, ICH guidelines, Forced degradationAbstract
Objective: To develop a novel, simple, precise and stability indicating reverse phase ultra-performance liquid chromatographic (RP-UPLC) method and validate as per ICH guidelines for the quantification of R-Telaprevir in drug substance and pharmaceutical dosage form of Telaprevir.
Methods: The chromatographic separation was achieved with Acquity UPLC-BEH C-18 column (100 mm X 2.1 mm, 1.7 μm particle size column with mobile phase containing a gradient mixture of Mobile phase-A and B, flow rate of 0.25 ml/min and a detection wavelength of 210 nm. Mobile phase-A contains a mixture of 10 mm di-Potassium hydrogen phosphate anhydrous, pH adjusted to 11.5 with potassium hydroxide and methanol in the ratio 85:15 (v/v) and the mobile phase-B contains a mixture of Acetonitrile, methanol, 2-propanol and ethanol in the ratio 80:10:7:3 (v/v/v/v) respectively. Chromatographic separation was achieved on UPLC in gradient elution mode by QbD with Design-of-Experiments approach.
Results: The method exhibited consistent, high-quality recoveries [100±10%] with a high precision for R-Telaprevir. Linear regression analysis revealed an excellent correlation between peak responses and concentrations (r2value of 0.9996) for R-Telaprevir. The method is sensitive enough to quantifyR-Telaprevir above 0.05% and detect above 0.015% in Telaprevir. Forced degradation studies proved that the method is specific for R-Telaprevir.
Conclusion: An accurate, precise, linear, robust and specific UPLC method was developed and validated for the quantification of R-Telaprevir in drug substance and pharmaceutical dosage form of Telaprevir as per ICH guidelines. The method is stability-indicating and can be used for routine analysis of production samples and to check the stability of samples.
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References
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