ABSTRACT
The stability of alprostadil diluted in 0.9% sodium chloride stored in polyvinyl chloride (VIAFLEX) containers at refrigerated temperature, protected from light, is reported. Five solutions of alprostadil 11 mcg/mL were prepared in 250 mL 0.9% sodium chloride polyvinyl chloride (PL146) containers. The final concentration of alcohol was 2%. Samples were stored under refrigeration (2°C to 8°C) with protection from light. Two containers were submitted for potency testing and analyzed in duplicate with the stability-indicating high-performance liquid chromatography assay at specific time points over 14 days. Three containers were submitted for pH and visual testing at specific time points over 14 days. Stability was defined as retention of 90% to 110% of initial alprostadil concentration, with maintenance of the original clear, colorless, and visually particulate-free solution. Study results reported retention of 90% to 110% initial alprostadil concentration at all time points through day 10. One sample exceeded 110% potency at day 14. pH values did not change appreciably over the 14 days. There were no color changes or particle formation detected in the solutions over the study period. This study concluded that during refrigerated, light-protected storage in polyvinyl chloride (VIAFLEX) containers, a commercial alcohol-containing alprostadil formulation diluted to 11 mcg/mL with 0.9% sodium chloride 250 mL was stable for 10 days.
Subject(s)
Alprostadil/chemistry , Drug Packaging , Excipients/chemistry , Platelet Aggregation Inhibitors/chemistry , Polyvinyl Chloride/chemistry , Sodium Chloride/chemistry , Vasodilator Agents/chemistry , Alprostadil/pharmacology , Alprostadil/radiation effects , Chromatography, High Pressure Liquid , Cold Temperature , Drug Compounding , Drug Stability , Drug Storage , Hydrogen-Ion Concentration , Isotonic Solutions , Light , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation Inhibitors/radiation effects , Sodium Chloride/radiation effects , Time Factors , Vasodilator Agents/pharmacology , Vasodilator Agents/radiation effectsABSTRACT
Ticagrelor is a direct-acting and reversible P2Y12-adenosine diphosphate (ADP) receptor blocker used as antiplatelet drug. Forced degradation under various stress conditions was carried out. The degradation products have been detected and identified by high-pressure liquid chromatography multistage mass spectrometry (LC-MS(n)) along with high-resolution mass spectrometry. C18 XTerra MS column combined with a linear gradient mobile phase composed of a mixture of 10 mM acetate ammonium/acetonitrile was shown suitable for drug and impurity determinations and validated as a stability indicating method. Structural elucidation of the degradation products relied on MS(n) studies and accurate mass measurements giving access to elemental compositions. Up to nine degradation products resulting from oxidation/auto-oxidation, S-dealkylation and N-dealkylation have been identified, covering a range of possible degradation pathways for derivatives with such functional groups. Kinetics was also studied in order to assess the molecule's shelf-life and to identify the most important degradation factors.
Subject(s)
Adenosine/analogs & derivatives , Chromatography, Reverse-Phase/methods , Mass Spectrometry/methods , Platelet Aggregation Inhibitors/analysis , Purinergic P2Y Receptor Antagonists/analysis , Adenosine/analysis , Adenosine/chemistry , Adenosine/radiation effects , Chromatography, Reverse-Phase/instrumentation , Drug Contamination , Drug Stability , Hot Temperature , Hydrolysis , Limit of Detection , Molecular Structure , Oxidation-Reduction , Photolysis , Platelet Aggregation Inhibitors/chemistry , Platelet Aggregation Inhibitors/radiation effects , Purinergic P2Y Receptor Antagonists/chemistry , Purinergic P2Y Receptor Antagonists/radiation effects , Reproducibility of Results , TicagrelorABSTRACT
The effect of ultraviolet (UV) or visible light (VIS) irradiation on the chemical stability of ethyl icosapentate [ethyl-(all-cis)-5,8,11,14,17-icosapentaenoate] (EPA) was investigated at 45 degrees C by means of HPLC and by measuring the peroxide value (POV). EPA was oxidized to peroxides after an induction period by photoirradiation, and the peroxide subsequently degraded to secondary products. The autoxidation of EPA followed consecutive reaction kinetics including an induction period, and the kinetic parameters of the oxidation were calculated based upon the consecutive reaction model by computer curve fitting. The results of the degradation rate constant, k, and the induction period obtained by HPLC showed that the radical and the peroxide formation rates are affected by UV, but not by VIS light irradiation. The formation rate constant of peroxide, k1, and its degradation rate constant to secondary products, k2, obtained from the POV under UV light irradiation, increased with irradiation intensity, during which the induction period decreased. On the other hand, k1, k2 and the induction period by VIS light irradiation did not change significantly. The relationship between the induction periods obtained by HPLC and POV and the UV light irradiation energy were superimposed in the plots, indicating that these parameters depended on the UV irradiation energy. The relationship between k1/k2 ratio and the UV irradiation energy suggested that the formation of secondary products was more remarkably accelerated by UV energy than that of peroxide.
