Trace analysis of zotepine and its active metabolite in plasma by capillary electrophoresis with solid phase extraction and head-column field-amplified sample stacking

Chou, Yu-Wei; Huang, Wei-Shan; Chen, Cheng‐Chung; Lin, Shuo; Wu, Hsin‐Lung; Chen, Su‐Hwei

doi:10.1016/j.chroma.2004.11.061

Cited by 14 publications

(12 citation statements)

References 23 publications

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“…In one study conducted with 12 young healthy subjects, plasma concentration of norZTP was measured, and C max value of norZTP was approximately 30% of the parent compound in plasma (ZTP at 12.7 ng/ml versus norZTP at 3.79 ng/ml) after administration of 50 mg of ZTP (Velagapudi et al, 1997). Similar results were observed in a schizophrenia patient (Chou et al, 2005). These results suggest that norZTP may contribute considerably to the clinical therapeutic effects of its mother compound ZTP, provided norZTP is pharmacologically active.…”

supporting

confidence: 57%

Norzotepine, a Major Metabolite of Zotepine, Exerts Atypical Antipsychotic-Like and Antidepressant-Like Actions through Its Potent Inhibition of Norepinephrine Reuptake

Shobo

Yamada²,

Mihara³

et al. 2010

J Pharmacol Exp Ther

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The antipsychotic drug zotepine [ZTP;f]thiepin-10-yl)oxy]-N,N-dimethylethan-1-amine] is known to have not only atypical antipsychotic effects but also antidepressive effects in schizophrenia patients. Norzotepine [norZTP;f]thiepin-10-yl)oxy]-N-methylethan-1-amine] has been postulated to be a major metabolite of ZTP in humans. Here, we characterized norZTP through several in vitro studies and in animal models of psychosis, depression, and extrapyramidal symptoms (EPS) and compared the pharmacological profiles with those of ZTP. Although both compounds showed similar overall neurotransmitter receptor binding profiles, norZTP showed 7-to 16-fold more potent norepinephrine reuptake inhibition than ZTP. In a pharmacokinetic study, both ZTP and norZTP showed good brain permeability when administered individually in mice, although norZTP was not detected in either plasma or brain after intraperitoneal injection of ZTP. In the methamphetamineinduced hyperlocomotion test in mice, norZTP and ZTP showed similar antipsychotic-like effects at doses above 1 mg/kg i.p. In contrast, unlike ZTP, norZTP did not induce catalepsy up to 10 mg/kg i.p. norZTP significantly antagonized the hypothermia induced by reserpine [(3␤,16␤,17␣,18␤,20␣)-11,17-dimethoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]yohimban-16-carboxylic acid methyl ester], suggesting in vivo inhibition of the norepinephrine transporter. In the forced-swim test, norZTP exerted an antidepressant-like effect at the effective doses for its antipsychotic action, whereas ZTP neither antagonized reserpine-induced hypothermia nor showed antidepressant-like effect. These results collectively demonstrate that norZTP exerts more potent inhibitory action than ZTP on norepinephrine transporters both in vitro and in vivo, presumably accounting for its antidepressant-like effect and low EPS propensity. Given that norZTP is the major metabolite observed in humans, norZTP may contribute to the unique clinical profiles of its mother compound, ZTP.

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supporting

confidence: 57%

Norzotepine, a Major Metabolite of Zotepine, Exerts Atypical Antipsychotic-Like and Antidepressant-Like Actions through Its Potent Inhibition of Norepinephrine Reuptake

Shobo

Yamada²,

Mihara³

et al. 2010

J Pharmacol Exp Ther

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“…We could also provide sensitivity enhancement by various approach, for example, head-column field-amplified sample stacking in binary system. 17 Furthermore, CE will not produce as much waste and pollutants as HPLC does during the experimental procedure (Table 4). Both Musenga et al and our study found that CE method may be used to detect aripiprazole.…”

Section: Discussionmentioning

confidence: 99%

“…8 CE was also used in detecting zotepine with solid-phase extraction and binary system of head-column field-amplified sample stacking method. 17 Raggi used a rapid CE method for the determination of clozapine and desmethylclozapine in human plasma and it proved to have good precision. 20 Studies on using CE method for analysis of aripiprazole and its metabolites were limited.…”

Section: Introductionmentioning

confidence: 99%

The quantitative detection of aripiprazole and its main metabolite by using capillary-electrophoresis

Tsai

Yu²,

Chiu³

et al. 2011

Journal of the Chinese Medical Association

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“…One study has found that detection of this compound from plasma was possible at the micromolar level [111]. A drug like zotepine and its active metabolite, norzotepine, have been detected in plasma using CE [112]. Amphetamine and p-hydroxymethamphetamine are the metabolites of methamphetamine, which is used in obesity treatment.…”

Section: Ce In Metabolomicsmentioning

confidence: 98%

CE at the omics level: Towards systems biology – An update

Song

Babar

et al. 2007

Electrophoresis

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This review provides an updated overview of recent developments and applications of CE based on previously published reports in the field of omic research. The increased number of published articles on omics shows that the field is growing and attracting the attention of many life science researchers. Due to developments in the omics sciences, many researchers have been studying systems biology, in which biological events in organisms are systematically interpreted through the combination of complex measurements from various methods resulting in high-throughput data. Given the challenges of such complex forms of analysis, CE is a strong candidate for generating omics data useful for acquiring the qualitative and quantitative knowledge necessary for systems-level investigation. By emphasizing CE for systems biology, this review will discuss and focus on the applicability of CE to systems-based analytical data at the genomic, transcriptomic, proteomic, and metabolomic levels from 2005 to the present.

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Trace analysis of zotepine and its active metabolite in plasma by capillary electrophoresis with solid phase extraction and head-column field-amplified sample stacking

Cited by 14 publications

References 23 publications

Norzotepine, a Major Metabolite of Zotepine, Exerts Atypical Antipsychotic-Like and Antidepressant-Like Actions through Its Potent Inhibition of Norepinephrine Reuptake

Norzotepine, a Major Metabolite of Zotepine, Exerts Atypical Antipsychotic-Like and Antidepressant-Like Actions through Its Potent Inhibition of Norepinephrine Reuptake

The quantitative detection of aripiprazole and its main metabolite by using capillary-electrophoresis

CE at the omics level: Towards systems biology – An update

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