Simultaneous determination of olanzapine, clozapine and demethylated metabolites in serum by on-line column-switching high-performance liquid chromatography

Weigmann, Harald; Härtter, Sebastian; Maehrlein, Sabine; Kiefer, Werner; Krämer, Godehard; Dannhardt, Gerd; Hiemke, Christoph

doi:10.1016/s0378-4347(01)00215-8

Cited by 63 publications

(35 citation statements)

References 49 publications

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“…These values are reported here. The levels of fluvoxamine and clozapine were analysed using HPLC with oxaprotiline or fluperlapine respectively as internal standards (Hartter et al, 1992 ;Weigmann et al, 2001). The level of haloperidol was determined using a liquid chromatography (LC) system coupled with mass spectrometry in the laboratory of Professor Zernig at Innsbruck, Germany.…”

Section: Drug Level Determinationmentioning

confidence: 99%

“…PKCb, GABA-A Rb3 and PKCc were increased significantly also by fluvoxamine (4.8-, 2.8-, and 8-fold over control, respectively). The combined treatment had no statistically significant effects on The levels of fluvoxamine and clozapine were analysed by HPLC (Hartter et al, 1992 ;Weigmann et al, 2001) and of haloperidol by tandem mass spectrometry (Zernig et al, 2004). The values are given as average of six rats (¡S.E.M.)…”

Section: Mrna Expression Analysis In Rat Frontal Cortexmentioning

confidence: 99%

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The effect of chronic co-administration of fluvoxamine and haloperidol compared to clozapine on the GABA system in the rat frontal cortex

Chertkow

Weinreb²,

Youdim³

et al. 2005

Int. J. Neuropsychopharm.

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Clinical studies in schizophrenia patients have shown that adding a selective serotonin reuptake inhibitor (SSRI) to antipsychotics can ameliorate negative symptoms that frequently resist standard treatments. It has been proposed that this combined treatment produces a 'net effect', different from that of the individual drugs and possibly common to that of the atypical antipsychotic, clozapine, which also ameliorates negative symptoms. The present study was initiated to determine the molecular events in the rat frontal cortex resulting from combined treatment of fluvoxamine and haloperidol compared to clozapine. Rats were allocated to five groups and received a daily intraperitoneal injection with one of the following : haloperidol (1 mg/kg), fluvoxamine (11 mg/kg), clozapine (11 mg/kg), haloperidol (1 mg/kg) plus fluvoxamine (11 mg/kg), or vehicle for 30 d. cDNA arrays were used to screen a broad range of genes in the frontal cortex. Several of the most prominent alterations were taken for analysis in real-time RT-PCR and their related proteins were examined by the Western-blotting technique. The gene expression profile of the combined fluvoxamine plus haloperidol treatment was different from that of the individual drugs. Moreover, clozapine showed some degree of homology with the dual treatment. The protein expression changes, specific to the combined treatment, included glutamic acid decarboxylase (GAD67) and protein kinase Cb (PKCb). The latter showed a similar trend following clozapine treatment. The present findings support the existence of a unique mechanism for SSRI-antipsychotic combination, different from that of the individual drugs and suggest that it may involve modification of the gamma aminobutyric acid (GABA) system.

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Section: Drug Level Determinationmentioning

confidence: 99%

Section: Mrna Expression Analysis In Rat Frontal Cortexmentioning

confidence: 99%

The effect of chronic co-administration of fluvoxamine and haloperidol compared to clozapine on the GABA system in the rat frontal cortex

Chertkow

Weinreb²,

Youdim³

et al. 2005

Int. J. Neuropsychopharm.

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“…After clean-up, a six-port valve is switched to connect the clean-up column with the analytical column. Using column switching with an on-line sample clean-up may be even more advantageous, since it enables automated sample analysis for routing clinical samples (Weigmann et al, 2001;Sachse et al, 2003Sachse et al, , 2006Yasui-Furukori et al, 2004;Kollroser and Schober, 2002;Olesen and Poulsen, 1993). Weigmann et al (2001) used a cyanopropyl (CPS) coated column (10 μm; 10 × 2.0 mm i.d.)…”

Section: High-performance Liquid Chromatographymentioning

confidence: 99%

Bioanalytical methods for the determination of antipsychotic drugs

Zhang

Terry

Bartlett

2008

Biomedical Chromatography

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Antipsychotic drugs are popular for the treatment of schizophrenia and other psychoses. In general, antipsychotics are administered in oral doses of only a few milligrams per day and they are widely metabolized in the body. Therefore, the concentration of these drugs in plasma is very low (pg-ng/mL levels). In addition, therapeutic drug monitoring (TDM) of antipsychotic drugs has proven to be of notable value for determining poor compliance of patients and addressing the challenges associated with considerable genetic variability in their metabolism. Thus, in order to conduct pharmacology and toxicology studies and clinical TDM of antipsychotics, as well as address the challenges associated with polypharmacy and drug metabolism, highly sensitive, selective and accurate bioanalytical methods are essential. The most recent studies on the determination of antipsychotics will be reviewed, including separation techniques, sample pretreatment, detectors and validation.

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“…Dès lors, le dosage de ce médicament s'avère utile dans le diagnostic Correspondance : Hassen Teyeb, teyeb.hassen@gmail.com d'une intoxication aiguë et la prise en charge du patient, ou dans un cadre médico-légal. Plusieurs méthodes ont été utilisées pour le dosage de la clozapine, telles que la chromatographie liquide haute performance (HPLC), la chromatographie gazeuse couplée à la spectrométrie de masse, la fluorimétrie, la voltamétrie, la densitométrie, et les méthodes électrophoré-tiques [5][6][7][8][9][10][11][12][13][14]. De même, de nombreuses méthodes spectrophotométriques ont été adaptées pour ce dosage [8,11,[15][16][17].…”

Section: Introductionunclassified

Évaluation d’une méthode de dosage de la clozapine par spectrophotométrie UV

Teyeb

Najjar

2011

Ann Toxicol Anal

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Résumé -La clozapine, principal neuroleptique indiqué dans le traitement de la schizophrénie résistante, est à l'origine de nombreux cas d'intoxications accidentelles ou volontaires, d'où l'intérêt de son dosage. Notre travail a pour objectif la mise au point d'une méthode de dosage permettant le diagnostic d'une intoxication par la clozapine. La méthode est basée sur la lecture de l'absorbance, à 365 nm, du produit de la réaction entre la clozapine et l'iode dans le dichlorométhane. Les résultats ont montré que cette méthode de dosage est linéaire de 15 à 400 mg/L (r = 0,995), avec une limite de détection de 10,42 mg/L. La précision et l'exactitude ont été meilleures dans la zone de 120 à 400 mg/L. Le rendement de l'extraction, par l'éther, à partir des urines est en moyenne de 77,7 %. Cette méthode permet le dosage de la clozapine dans les urines, les comprimés et dans les échantillons post mortem en cas d'intoxication mortelle à la clozapine. Mots clés : Clozapine, spectrophotométrie UV, dichlorométhane, iodeAbstract -Clozapine, the principal neuroleptic indicated in the treatment of resistant schizophrenia, is implicated in many cases of accidental or voluntary intoxications. Thus, this drug should be dosed. In this work, the dosage of clozapine by UV spectrophotometry was studied to perfect a method allowing the diagnosis of intoxication or an overdose. The method is based on the reading of the absorbance of the product of the reaction between clozapine and iodine in dichloromethane at 365 nm. The results showed that this method is linear from 15 to 400 mg/L (r = 0.995), with a detection limit of 10.42 mg/L. Precision and accuracy were better between 120 and 400 mg/L. The extraction yield, by ether, from urine is on average 77.7%. This method allows the dosage of clozapine in urine, tablets and in post mortem samples in the case of clozapine fatal intoxication.

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Simultaneous determination of olanzapine, clozapine and demethylated metabolites in serum by on-line column-switching high-performance liquid chromatography

Cited by 63 publications

References 49 publications

The effect of chronic co-administration of fluvoxamine and haloperidol compared to clozapine on the GABA system in the rat frontal cortex

The effect of chronic co-administration of fluvoxamine and haloperidol compared to clozapine on the GABA system in the rat frontal cortex

Bioanalytical methods for the determination of antipsychotic drugs

Évaluation d’une méthode de dosage de la clozapine par spectrophotométrie UV

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