title: Rapid resolution liquid chromatography for monitoring the quality of stockpiled atropine preparations for injection.
abstract: We describe a rapid resolution liquid chromatography (RRLC) method for analyzing atropine sulfate, its degradation products (tropic acid, apoatropine, atropic acid) and other components (e.g. phenol, methylparaben) in injectable medicines that are used by the German armed forces in emergency situations. Chromatography is performed using an acetonitrile/phosphate buffer gradient (pH = 1.0) and an RP 18 column (50 x 4.6 mm, 1.8 µm) with the detection wavelength set at 220 nm. The concentration of the active ingredient (atropine sulfate) in the tested products ranges from about 1 mg•ml(-1) to 10 mg•ml(-1) . The concentrations of the detected degradation products range from 0.2% to 4.7% (tropic acid) in relation to the active pharmaceutical ingredient (API). Using shorter separation columns and smaller particle sizes of the stationary phase improved analysis time from 40 to 10 min and reduced the consumption of solvents by approximately 75%. Owing to the pressure conditions (< 200 bar), UHPLC (ultra high performance liquid chromatography) systems are not needed. Comparison of the atropine and tropic acid results obtained with the previously used HPLC (high performance liquid chromatography) method of the MAH (marketing authorization holder) show that there is no indication of a significant difference between the two methods.
authors.affiliation: Central Institute of the Bundeswehr Medical Service Munich, Ingolstaedter Landstrasse 102, Garching Hochbrück, Germany. thomas2zimmermann@bundeswehr.org
authors.forename: Thomas
authors.initials: T
authors.lastname: Zimmermann
authors.forename: Andre
authors.initials: A
authors.lastname: Dimmel
authors.forename: Sandra
authors.initials: S
authors.lastname: Jüttemeyer
authors.forename: Dietmar
authors.initials: D
authors.lastname: Springer
authors.forename: Michael
authors.initials: M
authors.lastname: Loch
mesh_terms: D000931:Antidotes / Q000008:administration & dosage / Q000032:analysis*; D001285:Atropine / Q000008:administration & dosage / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid / Q000191:economics / Q000379:methods*; D004356:Drug Storage; D007267:Injections; D016014:Linear Models; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000032:analysis*; D004364:Pharmaceutical Preparations / Q000737:chemistry; D011786:Quality Control; D012680:Sensitivity and Specificity; D013997:Time Factors
chemical_list: D000931:Antidotes; D018727:Muscarinic Antagonists; D004364:Pharmaceutical Preparations; D001285:Atropine