AJAC  Vol.6 No.12 , November 2015
Validated Gradient Stability Indicating UPLC Method for the Determination of Related Substances of Posaconazole in Bulk Drug
Abstract: A stability-indicating UPLC method has been developed and validated for the determination of related substances of Posaconazole with its four related substances (Hydroxytriazole, Tosylated compound, Deshydroxy posaconazole and Benzylated posaconazole) in the drug substance. Forthwith simple UPLC chromatographic separations were achieved on a Waters Acquity BEH shield C18 (100 mm length, 2.1 mm internal diameter and 1.7 μm particle size) with a mobile phase containing 0.1% Orthophosphoric acid (i.e. 1 mL in 1000 mL water) in gradient combination with acetonitrile (ACN) at a flow rate of 0.5 mL/min and the eluent were monitored at 210 nm. As a result, the resolution of Posaconazole from any of impurities was found to be greater than 2.0. The test solution and spiked solutions were found to be stable in the diluent for 48 h. For the purpose method to be stability indicating, forced degradation studies were conducted and the method resolved the drug from its known impurities, stated above, and from additional impurities generated when POS subjected to forced degradation; the mass balance was found close to 100%. Regression analyses indicate correlation coefficient value greater than 0.999 for Posaconazole and its known impurities. The LOD for Posaconazole and the known impurities was at a level below 0.05%. The method has shown good, consistent recoveries for known impurities (89% - 106%). To summarise, the method was found to be accurate, precise, linear, specific, sensitive, rugged, robust, and stability-indicating.
Cite this paper: Prasad, V. , Reddy, V. and Aparna, P. (2015) Validated Gradient Stability Indicating UPLC Method for the Determination of Related Substances of Posaconazole in Bulk Drug. American Journal of Analytical Chemistry, 6, 965-976. doi: 10.4236/ajac.2015.612092.

[1]   (2014) Posanol (Posaconazole) Product Monograph, Merck Canada Inc.

[2]   Noxafil: EPAR—European Medicines Agency-Europa Annex I Summary of Product Characteristics.

[3]   Schering Corporation (2009) Noxafil (Posaconazole) Oral Suspension Prescribing Information. Kenilworth.

[4]   Keating, G.M. (2005) Posaconazole. Drugs, 65, 1553-1569.

[5]   Torres, H.A., Hachem, R.Y., Chemaly, R.F., et al. (2005) Posaconazole: A Broad-Spectrum Triazole Antifungal. The Lancet Infectious Diseases, 5, 775-785.

[6]   Dodds Ashley, E.S., Varkey, J.B., Krishna, G., et al. (2009) Pharmacokinetics of Posaconazole Administered Orally or by Nasogastric Tube in Healthy Volunteers. Antimi-crobial Agents and Chemotherapy, 53, 2960-2964.

[7]   ICH (2003) Stability Testing of New Drug Substances and Products. Q1A (R2).

[8]   ICH (2006) Impurities in New Drug Substances. Q3A (R1).

[9]   ICH (2006) Impurities in New Drug Products. Q3B (R1).

[10]   Reddy, S.K., Govind, N.Ch.V.S., Rajan, S.T., Eshwaraiah, S., Chakravarthy, I.E., Rakesh, M. and Kishore, M. (2014) Stability Indicating HPLC Method for the Quantification of Posaconazole and Its Related Substances. Der Pharma Chemica, 6, 486-494.

[11]   Triazole Adverse Effects, Toxicity, and Safety Russell Lewis. University of Houston College of Pharmacy, University of Texas, Anderson Cancer Center, Houston.

[12]   (2005) Validation of Analytical Procedures: Text and Methodology. Q2 (R1).

[13]   Singh, S. and Bakshi, M. (2002) Development of Stability Indicating Assay Methods—A Critical Review. Journal of Pharmaceutical and Biomedical Analysis, 28, 1011-1040.

[14]   Kathirvel, S., Raju, R., Seethadevi, B., Suneetha, A. and Pavani, J. (2014) Stability Indicating RP-HPLC Method for the Determination of Process Related Impurities in Posaconazole API. Asian Journal of Pharmacy and Technology, 4, 167-178.