Doxycycline hyclate (DOX) is an FDA-approved drug product for the use for postexposure prophylaxis (PEP) following exposure to aerosolized Bacillus anthracis. Based on national preparedness for chemical, biological, radiological, and nuclear emergencies and DOX indications for anthrax and acute radiation syndrome, a number of federal, state, and local public health and emergency response stakeholders stockpile doxycycline tablets or capsules as medical countermeasures (MCMs). Our previous published work has documented the challenges to efficiently implement the compendial method.  In recognition of the need and an effort to address the importance of the product quality of this critical stockpiled antibiotic in response to bioterrorism concerns, we have developed efficient robust analytical ultra-performance liquid chromatographic (UPLC) method for the simultaneous determination of doxycycline hyclate and its impurities metacycline, 4-epidoxycycline, and 6-epidoxycycline. The chromatography was performed on a Waters Acquity UPLC system using Waters Aquity BEH C18 (2.1 x 50mm, 1.7 µm) column maintained at 55 °C. Doxcycline and its degradation and synthetic impurities were eluted isocratically with 75mM ammonium acetate 4mM EDTA (pH 8.8) and acetonitrile (97:3) as the mobile phase with a flow rate of 1.2 mL/min, and ultraviolet detection at 270 nm. Baseline separation of the analytes was achieved in 6 minutes. In summary, a stability-indicating UPLC method was developed and validated after forced degradation studies were conducted on doxycycline hyclate under the conditions of oxidation, photolysis and hydrolysis (acid and basic). The developed method was found to be selective, robust, accurate, precise, and reproducible for the simultaneous quantitation of doxycycline hyclate and its degradation impurities. The method was successfully applied to the evaluation of marketed drug products.<br/>

Development and validation of stability-indicating ultra-performance liquid chromatography (UPLC) method for doxycycline hyclate drug products: An optimization of the USP compendial methodology

252nd National Meeting (2016)

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