Abstract
The rapid and accurate high-performance liquid chromatography method with ultraviolet detection (210 nm) for the determination of Ziprasidone in rat urine was developed. Simple protocol of solid-phase extraction of ziprasidone from urine sample at presence its main metabolites was worked out. Vardenafil was used as an internal standard. Reversed phase column LUNA® C18(2) 100A 250 mm × 4.6 mm × 5 μm was used with an isocratic mobile phase consisting of acetonitrile : 0.5 % triethylamine (30: 70) and 0.1 M phosphoric acid (pH 2.5). Developed conditions of HPLC analysis provide high efficiency of a system and good separation of analytes. The method was validated and applied to rat urine samples after modelling intoxication. The intra- and inter-day precision was ≤ 15% with recovery about 95 %. A linear range of 1 μg/mL to 200 μg/mL was established. LOD and LOQ were 0.2 and 0.5 μg/mL, respectively. Obtained results indicate that the described procedure of sample pretreatment with automatization possibility allows obtaining good results for ziprasidone. This method is sensitive, precise and repeatable enough to be used in toxicological casework.
Highlights
It was experimentally determined that the ziprasidone recovery from an aqueous solution after solid phase extraction was 97.5-98.2%
The efficiency of extraction of ziprasidonefrom urine was determined by analyzing model urine samples (n=9) with three levels of drug concentrations.The overall recovery of ziprasidone in the assay was above 95%
There is a clear separation of ziprasidone peaks with its metabolites in the chromatograms obtained from urine samples of laboratory rats (Figure 3)
Summary
Piperazinyl]ethyl]-6-chloro-1.3-dihydro-2H-indol-2-one) is widely used for the treatment of both positive and negative symptoms of schizophrenia (Shin et al, 2011; Strom et al., 2011;Pfizer Inc., 2014). The interaction with the 5-HT2A and 5-HT1A, 5-HT2c, 5-HT1D, 5HT7 receptors and type 2(D2) dopamine receptors ziprasidonehas antipsychotic, antidepressant and anxiolytic effects (Asif, 2016). In the case of overdose or combining it with drugs, which cause prolongation of the QT interval, the cardiotoxic effect of the drug is observed (WenzelSeifert et al, 2011; Timour et al, 2012; Beach et al, 2013; Leonard et al, 2013; Hasnain and Vieweg, 2014). Cardiovascular toxicity is the most frequent cause ofspecified or sudden cardiac death in patients with schizophrenia (Marano et al, 2011; Söderberg et al, 2016)
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