“…Instability is due to either hydrolysis, which yields tropine and tropic acid, or dehydration, which yields apoatropine. [5][6][7] Apoatropine may undergo further hydrolysis to atropic acid and tropanol (tropine), and dimerization of these compounds may produce belladonnine and isatropic acid, respectively. 7 However, dimerization of these compounds occurs only under either extreme conditions such as high temperatures or following long periods of time and not under normal storage conditions.…”
Section: Discussionmentioning
confidence: 99%
“…7 However, dimerization of these compounds occurs only under either extreme conditions such as high temperatures or following long periods of time and not under normal storage conditions. 6,7 Thus, the main pathway of instability in aqueous atropine solution is the hydrolytic reaction yielding tropine and tropic acid. 8 The stability of aqueous atropine sulfate is dependent on several variables.…”
Objective: A massive nerve agent attack may rapidly deplete in-date supplies of atropine. The authors considered using atropine beyond its labeled shelf life. The objective was to determine the stability of premixed injectable atropine sulfate samples with different expiration dates. Methods: This was an in-vitro study using gas chromatography and mass spectrometry (GC/MS). Four atropine solutions (labeled concentration of 400 mg/mL) ranging from in date to 12 years beyond expiration (exp) and an additional sample of atropine sulfate (labeled concentration of 2,000 mg/ mL) obtained from a World War II era autoinjector were assayed for atropine stability. Standards of atropine sulfate and tropine were prepared and quantified by GC/MS. Study samples were prepared by adding a buffer solution to free the base, extracting with an isopropanol/methylene chloride mixture and followed by evaporating the organic layer to dryness. Pentafluoropropionic anhydride and pentafluoropropanol were then added as derivatization reagents. Study samples were heated, the derivitization reagents were evaporated, and the remaining compound was reconstituted in ethyl acetate for injection into the GC/MS. Results: All solutions were clear and colorless. Atropine concentrations were as follows: in date, 252 mg/mL; 2001 exp, 290 mg/mL; 1999 exp, 314 mg/mL; 1990 exp, 398 mg/mL; and WW II specimen, 1,475 mg/mL. Tropine was found in concentrations of \10 mg/mL in all study samples. Conclusions: Significant amounts of atropine were found in all study samples. All samples remained clear and colorless, and no substantial amount of tropine was found in any study sample. Further testing is needed to determine clinical effect.
“…Instability is due to either hydrolysis, which yields tropine and tropic acid, or dehydration, which yields apoatropine. [5][6][7] Apoatropine may undergo further hydrolysis to atropic acid and tropanol (tropine), and dimerization of these compounds may produce belladonnine and isatropic acid, respectively. 7 However, dimerization of these compounds occurs only under either extreme conditions such as high temperatures or following long periods of time and not under normal storage conditions.…”
Section: Discussionmentioning
confidence: 99%
“…7 However, dimerization of these compounds occurs only under either extreme conditions such as high temperatures or following long periods of time and not under normal storage conditions. 6,7 Thus, the main pathway of instability in aqueous atropine solution is the hydrolytic reaction yielding tropine and tropic acid. 8 The stability of aqueous atropine sulfate is dependent on several variables.…”
Objective: A massive nerve agent attack may rapidly deplete in-date supplies of atropine. The authors considered using atropine beyond its labeled shelf life. The objective was to determine the stability of premixed injectable atropine sulfate samples with different expiration dates. Methods: This was an in-vitro study using gas chromatography and mass spectrometry (GC/MS). Four atropine solutions (labeled concentration of 400 mg/mL) ranging from in date to 12 years beyond expiration (exp) and an additional sample of atropine sulfate (labeled concentration of 2,000 mg/ mL) obtained from a World War II era autoinjector were assayed for atropine stability. Standards of atropine sulfate and tropine were prepared and quantified by GC/MS. Study samples were prepared by adding a buffer solution to free the base, extracting with an isopropanol/methylene chloride mixture and followed by evaporating the organic layer to dryness. Pentafluoropropionic anhydride and pentafluoropropanol were then added as derivatization reagents. Study samples were heated, the derivitization reagents were evaporated, and the remaining compound was reconstituted in ethyl acetate for injection into the GC/MS. Results: All solutions were clear and colorless. Atropine concentrations were as follows: in date, 252 mg/mL; 2001 exp, 290 mg/mL; 1999 exp, 314 mg/mL; 1990 exp, 398 mg/mL; and WW II specimen, 1,475 mg/mL. Tropine was found in concentrations of \10 mg/mL in all study samples. Conclusions: Significant amounts of atropine were found in all study samples. All samples remained clear and colorless, and no substantial amount of tropine was found in any study sample. Further testing is needed to determine clinical effect.
“…Because of their therapeutical value, there is a need to develop rapid, sensitive, and accurate analytical methods for the analysis of these alkaloids, both in pharmaceutical preparations and in plant extracts. Several chromatographic methods, including thin layer chromatography [2], gas chromatography (GC) [3,4] and high performance liquid chromatography (HPLC) [5,6], as well as combined techniques such as GC-mass spectrometry (GC-MS) [7] and HPLC-MS [8] have been developed for the analysis of tropane alkaloids. Due to its high efficiency, flexibility, accuracy, and very high resolution, capillary electrophoresis (CE) has revealed an enormous separation potential for the analysis of plant secondary metabolites [9].…”
Capillary zone electrophoresis, coupled to UV and interfaced with electrospray ionization mass spectrometry (ESI‐MS), is described for the simultaneous analysis of hyoscyamine and scopolamine. On‐line UV detection occurred at 22 cm from the inlet of the capillary and ESI‐MS monitoring was performed along the entire length of the capillary (85 cm). An alkaline solution of 40 mM ammonium acetate at pH 8.5 was suitable for the analysis of the alkaloids under consideration. Under the optimized conditions, including CE and ESI‐MS parameters, the two alkaloids were resolved within a short time and with very high sensitivity. The differentiation of hyoscyamine and its positional isomer littorine, commonly encountered in plant material, is also presented using up‐front collision‐induced dissociation. Finally, the developed method was applied to the analysis of these alkaloids in Belladonna leaf extract and in Datura candida x D. aurea hairy root extract.
Because of the constantly increasing demand for optically pure drugs it is of great importance to elucidate factors affecting stereochemistry, in order to provide a stable formulation with a high chiral quality of the desired isomer. Therefore, the effects of cyclodextrins (CyDs) and their alkylated and hydroxyakylated derivatives on racemization and hydrolysis of (-)-(S)-hyoscyamine and (-)-(3-scopolamine were examined kinetically and spectroscopically (NMR). Direct methods, based on a chiral and achiral chromatographic phase system, were used to determine their degradation products and enantiomer composition during stability tests. All different CyDs, except a-CyD, retarded racemization and hydrolysis. The inclusion of the drug substances in CyDs inhibits the attack of hydroxyl ions andor water molecules and thus retards the racemization and hydrolysis. The racemization of the tropic acid alkaloids is dependent on the pH and temperature. NMR studies were used to evidence the formation of a soluble 1: 1 complex in aqueous solution.0 1993 Wiley-Liss, Inc.
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