Assay for quantitation of clozapine and its metabolite N-desmethylclozapine in human plasma by high-performance liquid chromatography with ultraviolet detection

Edno, L.; Combourieu, I.; Cazenave, M.; Tignol, Jean-Pierre

doi:10.1016/s0731-7085(97)00048-4

Cited by 18 publications

(15 citation statements)

References 15 publications

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“…The results are usually good, but the instrumentation needed is very expensive and the sample pretreatments are laborious; thus they are not suitable for clinical routine analyses. Several papers use highperformance liquid chromatography (HPLC) with UV [5,6,8,[13][14][15][16][17][18][19][20][21][22][23] or electrochemical [24,25] detection. The sample pretreatment often consists of a liquid-liquid extraction [6,13,15,16,[19][20][21][22][23][24][25] or solid-phase extraction [5,8,[19][20][21].…”

Section: Introductionmentioning

confidence: 99%

An improved HPLC-ED method for monitoring plasma levels of clozapine and its active metabolites in schizophrenic patients

et al. 2000

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SummaryAn HPLC method with electrochemical detection has been developed for the determination ofclozapine and its main metabolites, desmethylclozapine and clozapine Noxide, in human plasma. An accurate pretreatment of the biological samples was implemented by means of solid phase extraction (SPE) on HLB cartridges. This improved pretreatment, together with a new mobile phase, allows for the accurate determination of clozapine Noxide, which could not be quantitated by a previous method. The method uses only 100 #L of plasma for one complete analysis and shows good recovery values for all three analytes. The eluates from the SPE procedure were chromatographed in a reversed phase C 18 column using a mobile phase composed of phosphate buffer, acetonitrile and methanol. Clozapine, desmethylclozapine and clozapine N-oxide were eluted in less than 10 minutes, without any interference from the biological matrix. Linearity was observed over the 2.50 -150ng mL 1 (clozapine and desmethylclozapine) or 1.25 -75 ng mL 1 (clozapine N-oxide) range for the three analytes, with satisfactory repeatability values. The limit of detection 1 was 0.3 ng mL-for clozapine and desmethylclozapine, and 0.6 for clozapine N-oxide. The application to plasma samples of patients treated with Leponex gave good results. No interference from other common central nervous system drugs was found. This method seems to be a useful tool for pharmacokinetic studies and for clinical monitoring, because of its need for small plasma samples and its high sensitivity and selectivity.

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Section: Introductionmentioning

confidence: 99%

An improved HPLC-ED method for monitoring plasma levels of clozapine and its active metabolites in schizophrenic patients

et al. 2000

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“…For this reason reliable analytical methods for the monitoring of DMC, as well as CLZ plasma levels are a useful tool in drug safety management. Most methods for the analysis of this drug in human biological fluids are based on HPLC techniques with ultraviolet [11][12][13][14][15][16][17][18][19][20][21][22] or electrochemical [23,24] detection, usually after liquid-liquid extraction. These methods are laborious, time-consuming and tedious, especially the…”

Section: Introductionmentioning

confidence: 99%

Development and validation of an HPLC method for the simultaneous determination of clozapine and desmethylclozapine in plasma of schizophrenic patients

et al. 1999

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SummaryA high-performance liquid chromatographic method with amperometric detection has been developed for the determination of levels of clozapine (CLZ) and its active metabolite N-desmethylclozapine (DMC) in human plasma. The analysis was performed on a 5 ~m C8 reversed phase column (150 x 4.6 mm i.d.), with acetonitrile-phosphate buffer (pH 3.5), as the mobile phase. The detection voltage was +800 mV and the cell and column temperature were 50 ~ Linear responses were obtained between 2 ng mL -1 and 100 ng mL 1. Absolute recovery for both clozapine and desmethylclozapine exceeded 88 % and the detection limit was 1 ng mL -1. Repeatability, intermediate precision and accuracy were satisfactory. The method, which is rapid, sensitive and selective, has been applied to therapeutic drug monitoring in schizophrenic patients following administration of Leponex | tablets. In 21 patients in steady state at a mean daily clozapine dosage of 358 mg (ranging from 150 to 500 mg day-l), clozapine levels averaged 379 ng mL -~ (ranging from 102 to 818 ng mL -1) and DMC levels averaged 233 ng mL -1 (ranging fi'om 70 to 540 ng mL-1). The method requires only a very small amount of plasma (100 ~L), and thus it is suitable for pharmacokinetic studies, as well as for therapeutic drug monitoring.

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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

“…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). La limite de détection est compatible avec la surveillance thérapeutique.…”

Section: Discussionunclassified

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

et al. 2000

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Assay for quantitation of clozapine and its metabolite N-desmethylclozapine in human plasma by high-performance liquid chromatography with ultraviolet detection

Cited by 18 publications

References 15 publications

An improved HPLC-ED method for monitoring plasma levels of clozapine and its active metabolites in schizophrenic patients

An improved HPLC-ED method for monitoring plasma levels of clozapine and its active metabolites in schizophrenic patients

Development and validation of an HPLC method for the simultaneous determination of clozapine and desmethylclozapine in plasma of schizophrenic patients

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

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