Comparative study of performances of UHPLC-MS/MS and HPLC/UV methods for analysis of ziprasidone and its main impurities

Abstract

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.

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

“…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].…”

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

“…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 ].…”

“…The methods available in the literature for the analysis of ZPS and its five impurities have a drawback that is mainly related to the complicated and time-consuming chromatographic analysis [ 4 , 5 ], the lack of sensitivity [ 6 ], the use of phosphate salt and trietylamine as mobile phase modifiers [ 7 ], which are not recommended because of their influence on the lifetime of the column and chromatographic system, or the use of equipment that is not easily accessible in routine drug quality control [ 9 ]. Moreover, the basic properties and significant polarity differences in these solutes pose additional challenges for their RP-HPLC separation and determination.…”