Ultra‐performance liquid chromatography tandem mass spectrometry for the rapid, simultaneous analysis of ziprasidone and its impurities

Abstract

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.

Development of HPLC method for rapid profiling of serotonin receptor ligands and their oxidative degradants

“…The obtained selectivity between ziprasidone and oxy-ziprasidone was improved by the developed method (α = 1.85) compared to UHPLC-DAD analysis (α = 1.12) in ref. [12]. In the case of the separation of aripiprazole and aripiprazole N-oxide, progress was also made compared to the HPLC analysis in ref.…”

“…The 4arylpiperazines such as aripiprazole and ziprasidone belong to atypical antipsychotics which are among the most effective drugs used in psychiatry in the therapy of schizophrenia, mania, or acute psychotic reactions [4][5]. Literature survey revealed that quanti cation of ziprasidone has been performed by spectrophotometry [6], thin layer chromatography (TLC) [7][8], capillary electrophoresis [9], and high-performance liquid chromatography (HPLC) [10][11][12][13]. The levels of aripiprazole and its main metabolite dehydroaripiprazole were measured using HPLC with UV detection [14][15], capillary-electrophoresis [16], ultraperformance liquid chromatography (UPLC), or gas chromatography coupled with mass spectrometry (GC-MS) [17][18].…”

Идентификация Биомаркеров Шизофрении С Помощью Методов Масс-Спектрометрии (Обзор Литературы)

“…MS является оптимальным методом для оценки метаболических трансформаций АП [46] и их влияния на определенные органы и ткани [47], определения концентрации АП в плазме крови [48] не только для клинической практики, но и в отношении случаев токсикологического анализа post mortem [49].…”

Development of Analytical Quality by Design Compliant Chaotropic Chromatography Method for Ziprasidone and Its Five Impurities Determination

“…However, the separation was performed with a mobile phase consisting of acetonitrile and buffer (aqueous KH 2 PO 4 solution with triethylamine). The same group developed the highly sensitive UHPLC-MS/MS gradient elution method for the simultaneous quantification of ZPS and its five impurities and with the possibility to characterize the unknown degradation product [ 8 ]. Finally, they have also published a comparative study of the performance of the UHPLC-MS /MS and HPLC-UV methods for the analysis of ZPS and its major impurities [ 9 ].…”