A thin-layer chromatographic method for simultaneous determination of ziprasidone and its main impurities was developed and validated. Separation of the examined compounds was performed on chromatographic plates precoated with silica gel 60F 254 and using toluene-methanol-glacial acetic acid, 7.5:0.5:0.5 (v/v/v) as mobile phase. Ascending development mode was performed in the twin-trough chromatographic chamber, which was presaturated with mobile phase vapors for 15 min. The developed chromatographic plates were dried in air and densitometrically scanned at the wavelengths of 250 and 320 nm. Regression coefficient (r≥0.992), recovery (94.94-106.70%), limit of quantification of impurities (25 ng band -1 equivalent to the 0.14% impurity level), and robustness were validated and found satisfactory. The developed method is convenient for quantitative analysis and the purity screening of ziprasidone in pharmaceutical formulations.
The separation and characterization of the unknown degradation product of second-generation antipsychotic drug ziprasidone are essential for defining the genotoxic potential of the compound. The aim of this study was to develop a simple UHPLC method coupled with tandem mass spectrometry (MS/MS) for chemical characterization of an unknown degradant, and the separation and quantification of ziprasidone and its five main impurities (I-V) in the raw material and pharmaceuticals. Chromatographic conditions were optimized by experimental design. The MS/MS fragmentation conditions were optimized individually for each compound in order to obtain both specific fragments and high signal intensity. A rapid and sensitive UHPLC-MS/MS method was developed. All seven analytes were eluted within the 7 min run time. The best separation was obtained on the Acquity UPLC BEH C (50 × 2.1 mm × 1.7 μm) column in gradient mode with ammonium-formate buffer (10 mm; pH 4.7) and acetonitrile as mobile phase, with the flow rate of 0.3 mL min and at the column temperature of 30°C. The new UHPLC-MS/MS method was fully validated and all validation parameters were confirmed. The fragmentation pathways and chemical characterization of an unknown degradant were proposed and it was confirmed that there are no structural alerts concerning genotoxicity.
Ziprasidone is the second generation antipsychotic drug with unique multipotent G-protein-coupled (GPCR) receptor binding profile. Since ziprasidone is a highly lipophilic and unstable compound, development of efficient method for a concurrent assay of ziprasidone and its main impurities was a very challenging task.
The UHPLC-MS/MS method that we developed for simultaneous determination of ziprasidone and its main impurities (BITP, Chloroethyl-chloroindolinone, Zip-oxide, Zip-dimer, and Zip-BIT) was compared with some other related HPLC-UV methods of our own and other authorship. An increase of the mobile phase pH value from 2.5 to 4.7 units in the examined analytical methods influenced elution order of the investigated compounds. It was found out that the UHPLC-MS/MS method is more selective and sensitive than the earlier developed HPLC-UV method. Similar to our earlier HPLC-UV method, the UHPLC-MS/MS method is linear with a correlation coefficient (r) above 0.99 for all the analysed compounds, but with a negligibly lower precision and accuracy. Finally, with shorter analysis time, smaller column size and reduction of solvent consumption, UHPLC-MS/MS is assumed as a greener method than HPLC-UV for the ziprasidone purity assay.
After transfer of the UHPLC-MS/MS method to the UHPLC-DAD system, suitability of the UHPLC-DAD method for routine control of ziprasidone and its main impurities is examined and confirmed based on the retained good selectivity, resolution and short analysis time.
The retention behaviour of scopolamine (hyoscine) and its related compounds (norhyoscine, atropine, homatropine, and noratropine) was investigated on the silica-based HPLC stationary phase. The retention of investigated tropane alkaloids was interpreted by using the Soczewiński-Wachtmeister equation. A high correlation between the retention parameter (log k) and lipophilicity (log P) (R = 0.9923) confirms the significant influence of hydrophobic interactions on the retention behaviour of the aforementioned compounds. It was found that by increasing the acetonitrile fraction, a decrease in retention of the more polar epoxide derivatives (scopolamine, norhyoscine) and an increase in retention of the more lipophilic derivatives (atropine, noratropine, homatropine) is obtained. The best separation of the tropane alkaloids was achieved by a simple procedure that involved a mobile phase composed of acetonitrile and 40 mM ammonium acetate/0.05% TEA, pH 6.5; 50:50 v/v. Selected conditions were assumed for the determination of scopolamine hydrochloride in the eye drops (Scopolamini hydrobromidum 0.25%). The method was validated and it was found as selective, sensitive, precise, accurate, and robust for the further qualitative analysis of the scopolamine-related compounds.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.