Abstract
The purpose of this study was to evaluate the impact of polystyrene divinylbenzene copolymer HPLC columns on the chromatographic performance of the USP compendial method for doxycycline hyclate. The compendial method was implemented based on the assessment of the chromatographic performance of six USP defined L21 polystyrene divinylbenzene HPLC columns. Modifications to the method were based on USP for chromatography. The method was validated for the determination of doxycycline hyclate and its impurities in commercially available drug products. A number of different polystyrene-divinylbenzene columns were tested and failed to provide selectivity for the resolution of doxycycline and its impurities. Separation was optimally achieved on an Agilent PLPR-S column (250 × 4.6 mm, 8 μm) by using an Agilent 1260 series HPLC system. Doxycycline hyclate and its impurities were eluted isocratically at a flow rate of 1 mL/min with mobile phase and detected at 270 nm. The column temperature was maintained at 60oC. The method was validated according to USP category I requirements for Assay. Validation acceptance criteria were met in all cases. The analytical range for doxycycline hyclate was 50 - 250 μg/mL and the linearity was r2 > 0.999 over three days. The method was determined to be specific. Both accuracy (95.1% - 102.4%) and precision (0.50% - 4.8%) were established across the analytical range for low, intermediate and high QC concentrations. Method applicability was demonstrated by analyzing marketed products of doxycycline hyclate, in which results showed potency meeting USP acceptance criteria. In conclusion, this study described the remarkable differences in selectivity that were encountered during the implementation phase for the compendial methods for doxycycline and its impurities in marketed products and it could be used in the future to assss the product quality of doxycycline hyclate capsules stored in the National stockpiles.
Highlights
Doxycycline hyclate is a bacteriostatic tetracycline antibiotic and is prescribed primarily for the treatment of urinary, respiratory, and gastrointestinal tract infections
To select a column that will allow for the efficient implementation of a compendial method, the analyst must try to decide among type A or B silica, chemical selectivity, particle size, particle shape, steric interactions, and hydrophobicity to name just a few factors that can impact the performance of the liquid chromatographic method
The doxycycline hyclate capsule samples were received from the FDA, Center for Drug and Evaluation Research’s (CDER) Office of Counter-Terrorism and Emergency Coordination (OCTEC). 2-methylpropan-2-ol, disodium edetate, sodium hydroxide, and tetrabutylammonium hydrogen sulfate were purchased from Sigma-Aldrich
Summary
Doxycycline hyclate is a bacteriostatic tetracycline antibiotic and is prescribed primarily for the treatment of urinary, respiratory, and gastrointestinal tract infections. It is a first response medication indicated for Acute Radiation Syndrome (ARS). Because of these differences, small changes in pH or the organic component of the mobile phase can result in major differences in the hydrophobicity of the packing and the selectivity. For columns such as divinylbenzene that contain the copolymer, the degree of cross-linking can significantly affect the hydrophobic interactions and the overall selectivity. The purpose of this study is to identify factors that can impact the efficient implementation of compendial methods for stockpiled drug products such as doxycycline
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