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Development and Validation of a GC-MS Method for the Detection and Quantification of Clotiapine in Blood and Urine Specimens and Application to a Postmortem Case.

Mannocchi G, Pantano F, Tittarelli R, Catanese M, Umani Ronchi F, Busardò FP - Int J Anal Chem (2015)

Bottom Line: Methadone-d9 was used as internal standard.Results.Conclusions.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, Italy.

ABSTRACT
Introduction. Clotiapine is an atypical antipsychotic of the dibenzothiazepine class introduced in a few European countries since 1970, efficient in treatment-resistant schizophrenic patients. There is little published data on the therapeutic and toxic concentrations of this drug. Aims. The aim of the present study is the development and validation of a method that allows the detection and quantification of clotiapine in blood and urine specimens by gas chromatography-mass spectrometry (GC-MS). Methods. Validation was performed working on spiked postmortem blood and urine samples. Samples were extracted with liquid-liquid extraction (LLE) technique at pH 8.5 with n-hexane/dichloromethane (85/15 v/v) and analysis was followed by GC-MS. Methadone-d9 was used as internal standard. Results. The limit of detection (LOD) was 1.2 and 1.3 ng/mL for urine and blood, respectively, while the lower limit of quantification (LLOQ) was 3.9 and 4.3 ng/mL, respectively. Linearity, precision, selectivity, accuracy, and recovery were also determined. The method was applied to a postmortem case. The blood and urine clotiapine concentrations were 1.32 and 0.49 μg/mL, respectively. Conclusions. A reliable GC-MS method for the detection and quantification of clotiapine in blood and urine samples has been developed and fully validated and then applied to a postmortem case.

No MeSH data available.


Chemical structures of clozapine and clotiapine.
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Related In: Results  -  Collection


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fig1: Chemical structures of clozapine and clotiapine.

Mentions: Clotiapine has been described as both typical and atypical antipsychotic in literature. It belongs to the dibenzothiazepine chemical class and was introduced in a few European countries since 1970. It is characterized by high incidence of extrapyramidal side effects, but some authors [1] underlie its efficacy in treating resistant schizophrenic patients. Its chemical structure is similar to that of clozapine; structural similarities are shown in Figure 1.


Development and Validation of a GC-MS Method for the Detection and Quantification of Clotiapine in Blood and Urine Specimens and Application to a Postmortem Case.

Mannocchi G, Pantano F, Tittarelli R, Catanese M, Umani Ronchi F, Busardò FP - Int J Anal Chem (2015)

Chemical structures of clozapine and clotiapine.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4508480&req=5

fig1: Chemical structures of clozapine and clotiapine.
Mentions: Clotiapine has been described as both typical and atypical antipsychotic in literature. It belongs to the dibenzothiazepine chemical class and was introduced in a few European countries since 1970. It is characterized by high incidence of extrapyramidal side effects, but some authors [1] underlie its efficacy in treating resistant schizophrenic patients. Its chemical structure is similar to that of clozapine; structural similarities are shown in Figure 1.

Bottom Line: Methadone-d9 was used as internal standard.Results.Conclusions.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, Italy.

ABSTRACT
Introduction. Clotiapine is an atypical antipsychotic of the dibenzothiazepine class introduced in a few European countries since 1970, efficient in treatment-resistant schizophrenic patients. There is little published data on the therapeutic and toxic concentrations of this drug. Aims. The aim of the present study is the development and validation of a method that allows the detection and quantification of clotiapine in blood and urine specimens by gas chromatography-mass spectrometry (GC-MS). Methods. Validation was performed working on spiked postmortem blood and urine samples. Samples were extracted with liquid-liquid extraction (LLE) technique at pH 8.5 with n-hexane/dichloromethane (85/15 v/v) and analysis was followed by GC-MS. Methadone-d9 was used as internal standard. Results. The limit of detection (LOD) was 1.2 and 1.3 ng/mL for urine and blood, respectively, while the lower limit of quantification (LLOQ) was 3.9 and 4.3 ng/mL, respectively. Linearity, precision, selectivity, accuracy, and recovery were also determined. The method was applied to a postmortem case. The blood and urine clotiapine concentrations were 1.32 and 0.49 μg/mL, respectively. Conclusions. A reliable GC-MS method for the detection and quantification of clotiapine in blood and urine samples has been developed and fully validated and then applied to a postmortem case.

No MeSH data available.