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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.


SIM mode chromatogram showing methadone-d9 (m/z: 303) and clotiapine (m/z: 343) in blood sample.
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fig4: SIM mode chromatogram showing methadone-d9 (m/z: 303) and clotiapine (m/z: 343) in blood sample.

Mentions: Afterwards, toxicological analysis, using the validated method described here, retrieved the following concentrations: 1.32, 0.49, and 1.85 μg/mL in peripheral blood, urine, and gastric contents, respectively. No other drugs or alcohol was detected in biological samples. Full scan mode chromatograms and mass spectra as well as SIM mode chromatograms, indicating clotiapine and methadone-d9, obtained from the analysis of the blood sample, are given in Figures 3 and 4, respectively. In Figure 3, the peaks of extracted ions that were used for qualitative and quantitative analysis of clotiapine (m/z 209-244-343) are presented. The retention time of clotiapine as shown in the same figure is 8.755 minutes. In Figure 4, SIM mode chromatograms of analytes of interest (m/z: 303 for methadone-d9 and m/z: 343 for clotiapine) are given. The retention times recorded for methadone-d9 and clotiapine are 6.461 and 8.762, respectively.


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)

SIM mode chromatogram showing methadone-d9 (m/z: 303) and clotiapine (m/z: 343) in blood sample.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: SIM mode chromatogram showing methadone-d9 (m/z: 303) and clotiapine (m/z: 343) in blood sample.
Mentions: Afterwards, toxicological analysis, using the validated method described here, retrieved the following concentrations: 1.32, 0.49, and 1.85 μg/mL in peripheral blood, urine, and gastric contents, respectively. No other drugs or alcohol was detected in biological samples. Full scan mode chromatograms and mass spectra as well as SIM mode chromatograms, indicating clotiapine and methadone-d9, obtained from the analysis of the blood sample, are given in Figures 3 and 4, respectively. In Figure 3, the peaks of extracted ions that were used for qualitative and quantitative analysis of clotiapine (m/z 209-244-343) are presented. The retention time of clotiapine as shown in the same figure is 8.755 minutes. In Figure 4, SIM mode chromatograms of analytes of interest (m/z: 303 for methadone-d9 and m/z: 343 for clotiapine) are given. The retention times recorded for methadone-d9 and clotiapine are 6.461 and 8.762, respectively.

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.