The Assay of Clozapine and N-Desmethylclozapine in Human Plasma by High-Performance Liquid Chromatography

Lovdahl, Michael; Perry, Paul J.; Miller, Del D.

doi:10.1097/00007691-199101000-00010

Cited by 67 publications

(24 citation statements)

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“…Serum clozapine and demethylclozapine concentrations were determined by high-performance liquid chromatography with ultraviolet detection, using protriptyline as an internal standard (Haring et al 1988;Lovdahl et al 1991). The limit of quantitation was 50…”

Section: Methodsmentioning

confidence: 99%

“…Blood samples for meesurement of serum clozapine and demethylclozapine were taken 12 hr after the previous dose. The clozapine dosage of each patient was stable for at least two weeks before the sample was taken.Serum clozapine and demethylclozapine concentrations were determined by high-performance liquid chromatography with ultraviolet detection, using protriptyline as an internal standard (Haring et al 1988;Lovdahl et al 1991). The limit of quantitation was 50…”

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confidence: 99%

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Clozapine Serum Concentrations are Lower in Smoking than in Non‐Smoking Schizophrenic Patients

Seppälä

Leìnonen

Lehtonen

et al. 1999

Pharmacology & Toxicology

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Serum concentrations of clozapine and its main metabolite demethylclozapine were measured in 44 schizophrenic inpatients, of whom ten were non-smokers and 34 smokers. When comparing their clozapine dose and body weightrelated serum drug levels, we found that clozapine and demethylclozapine concentrations were about 40Yn lower in the smoking than in the non-smoking group, probably due to an inducing effect of smoking on the cytochrome P450 (CYP) 1A2, which is involved in the metabolism of clozapine. We conclude that dosage adjustment may be necessary in clozapinetreated smokers.Clozapine, an atypical antipsychotic agent, is a well-established alternative in the treatment of treatment-refractory or neuroleptic-intolerant schizophrenic patients (Byerly & DeVane 1996).Clozapine is metabolised to demethylclozapine (norclozapine) and clozapine N-oxide in the liver. The pharmacological activity of these metabolites has been reported to be much lower than that of the parent drug (Jann et al. 1993). CYPIA2 and CYP3A4 are the primary enzymes involved in biotransformation of clozapine in vitro (Eiermann et al. 1997; Fang et al. 1998). In a recent study, the CYPlA2 inhibitor fluvoxamine considerably increased serum clozapine concentrations in schizophrenic patients (Wetzel et al. 1998). In contrast, the potent CYP3A4 inhibitor itraconazole did not affect the pharmacokinetics of clozapine in healthy volunteers (Raaska & Neuvonen 1998), suggesting that CYPlA2 is the principal CYP enzyme mediating the biotransformation of clozapine in humans (Bertilsson et al. 1994). On the other hand, serum clozapine levels can be decreased by drugs inducing CYP enzymes such as carbamazepine (Raitasuo et al. The aim of the present study was to compare dose-and weight-related serum clozapine and demethylclozapine concentrations between smoking and non-smoking schizophrenic patients in Finland. Materials and MethodsSubjects. Steady-state serum concentrations of clozapine and demethylclozapine were measured in 44 schizophrenic inpatients ( 3 1 men and 13 women) in the Tampere University Hospital. The diagnosis was established clinically by two experienced psychiatrists. All patients had received a fixed dosage of clozapine for at least two weeks prior to the study. Patients using drugs possibly affecting serum clozapine concentrations (e.g. omeprazole, selective serotonin reuptake inhibitors (SSRI) and inducers of CYP enzymes such a s carbamazepine) were not included (Centorrino et al. 1996; Spina r f al. 1998). Thirty-four patients (26 men and 8 women) were smokers and 10 (5 men and 5 women) were non-smokers (see table 1 for the characteristics of these two groups). The smokers consumed 10 40 cigarettedday (average 18.0 cigarettedday). The number of cigarettes smoked was counted by the nursing staff.Medication. Clozapine dosage was adjusted according to the therapeutic response and possible side effects. The individual dosage ranged from 150 to 800 mg/day and averaged 5 2 0 t 150 mg/day. The non-smoking patients received lower clozap...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Clozapine Serum Concentrations are Lower in Smoking than in Non‐Smoking Schizophrenic Patients

Seppälä

Leìnonen

Lehtonen

et al. 1999

Pharmacology & Toxicology

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“…Le mode isocratique est celui qui est classiquement utilisé (19)(20)(21)(22)(23). L'utilisation d'une colonne C8, d'une phase mobile à pH faiblement acide et d'une tempéra-ture de colonne de l'ordre de 60° C permet le dosage de la clozapine dans les procédures de routine du laboratoire (21,24).…”

Section: Discussionunclassified

Suivi toxicocinétique de la clozapine : étude d'une tentative de suicide

et al. 2000

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“…There are several methods published for the analyses of Clozapine and its metabolites using gas chromatography (GC) (3)(4)(5), GC-mass spectrometry (GCMS) (6)(7)(8), liquid chromatography (LC) (9) and high performance liquid chromatography (HPLC) (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). All aforementioned methods are often laborious, use tedious extraction procedures and have long run times with varying accuracies and precision.…”

Section: Introductionmentioning

confidence: 99%

Rapid liquid chromatography/tandem mass spectrometer (LCMS) method for clozapine and its metabolite N‐desmethyl Clozapine (Norclozapine) in human serum

Rao

Snyder

Vallaro

2009

Clinical Laboratory Analysis

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Clozapine is indicated for the treatment of schizophrenia and related psychotic disorders. Several methods have been developed for monitoring Clozapine levels; however, they possess limited specificity and are often laborious. This study describes a simple liquid chromatography/tandem mass spectrometer (LCMS) method in human serum. The ion transitions monitored were m/z 327, 270, 296 for Clozapine, m/z 313, 192, 227 for Norclozapine and m/z 328, 271 for Loxapine. The assay is linear (25-1000 ng/ml) and showed a good correlation (r=0.98) within the analytical range of 79-1210 ng/ml in human serum. This assay is highly specific and sensitive for the simultaneous measurements of Clozapine and Norclozapine. The simplification of this assay makes it ideal for high throughput analyses of the patient samples in a routine clinical laboratory staffed with general medical technologists.

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The Assay of Clozapine and N-Desmethylclozapine in Human Plasma by High-Performance Liquid Chromatography

Cited by 67 publications

References 0 publications

Clozapine Serum Concentrations are Lower in Smoking than in Non‐Smoking Schizophrenic Patients

Clozapine Serum Concentrations are Lower in Smoking than in Non‐Smoking Schizophrenic Patients

Suivi toxicocinétique de la clozapine : étude d'une tentative de suicide

Rapid liquid chromatography/tandem mass spectrometer (LCMS) method for clozapine and its metabolite N‐desmethyl Clozapine (Norclozapine) in human serum

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