Abstract
The development and implementation of advanced analytical technologies is essential for extending the expiry for complex drug products stored in the Strategic National Stockpiles. Consequently, a novel Ultra High-Performance Liquid Chromatographic (UHPLC) method has been developed for the analysis of atropine and its respective impurities to support the analytical research platform for auto-injectors. This study is part of a larger research effort to improve the efficiency and broaden the applicability of advanced analytical methods for medical counter-measure medications. The current HPLC compendial methodology for atropine sulfate injection requires an analysis time of 40 minutes for atropine. In comparison, the novel gradient UHPLC method required only 8 minutes to evaluate both atropine and its major pharmaceutical impurities. Improved separation was achieved on a Waters Acquity UHPLC BEH C18 1.7 μm, 2.1 × 100 mm column employing gradient elution of mobile phase solvent A (0.1% H3PO4) and solvent B (0.1% H3PO4, 90% ACN, and 10% H2O). The method was validated according to USP Category I requirements for assay. The daily standard calibration curves were linear over a concentration range from 50 μg/mL to 250 μg/mL with a correlation coefficient of >0.999. The detection limit (LOD) and quantitation limit (LOQ) were 3.9 μg/ml and 13.1 μg/ml, respectively. Resolution results indicate that atropine and the following impurities, degradants and a preservative can also be separated and analyzed using this proposed method: noratropine, 4,4’-di-hy-droxydiphenyl ether, 2,4’-dihydroxydiphenyl ether, 4-bromophenol, 4-hydro-xyatropine, tropic acid, apoatropine HCl, atropic acid, hydroquinone, nitroethane, phenol and catechol. The UHPLC method demonstrated enhanced selectivity and significantly reduced the analysis time when compared with the traditional USP compendial HPLC method. The method was successfully applied to the evaluation of atropine in ATNAA auto-injectors lots from the Strategic National Stockpiles.
Highlights
IntroductionThe Department of Defense (DoD) and Food and Drug Administration’s (FDA) Shelf Life Extension Program (SLEP) (http://www.fda.gov/EmergencyPreparedness/Counterterrorism/MedicalCounte rmeasures/MCMLegalRegulatoryandPolicyFramework/ucm411446.htm) represents a unique partnership between the DoD and the FDA’s Center for Drug and Evaluation Research (CDER) and the Office of Regulatory Affairs (ORA)
The Department of Defense (DoD) and Food and Drug Administration’s (FDA) Shelf Life Extension Program (SLEP) represents a unique partnership between the DoD and the FDA’s Center for Drug and Evaluation Research (CDER) and the Office of Regulatory Affairs (ORA)
The method was successfully applied for the analysis of atropine and its impurities in an auto-injector drug product
Summary
The Department of Defense (DoD) and Food and Drug Administration’s (FDA) Shelf Life Extension Program (SLEP) (http://www.fda.gov/EmergencyPreparedness/Counterterrorism/MedicalCounte rmeasures/MCMLegalRegulatoryandPolicyFramework/ucm411446.htm) represents a unique partnership between the DoD and the FDA’s Center for Drug and Evaluation Research (CDER) and the Office of Regulatory Affairs (ORA). This program is designed to save the federal government and the US taxpayer significant monetary resources by selecting products purchased by DoD and testing them for potency and stability to extend their effective shelf life beyond expiry. The FDA’s Detroit field laboratory has been an important partner with the Center for Drug Evaluation and Research in the analysis of various medical products stored (https://chemm.nlm.nih.gov/chempack.htm) for the DoD as part of the Strategic National Stockpile (SNS) program [3]
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