OBJECTIVE: To develop a method for determination of clozapine, olanzapine and mirtazapine in human plasma by liquid chromatography-tandem mass spectrometry(LC-MS/MS). METHODS: Clozapine, olanzapine and mirtazapine were extracted from plasma samples by using diethyl ether and separated by Agilent Zorbax SB-C18 column(2.1 mm x 150 mm, 5 microm). Electrospray ionization source was applied, positive ion mode was used to detect and multiple reaction monitoring mode was used to quantify clozapine, olanzapine and mirtazapine. Carbamazepine was the internal standard. RESULTS: The detection limits of clozapine, olanzapine and mirtazapine were within 0.41-0.92 ng/mL. The calibration curve in the concentration range of 10.0-2000.0 ng/mL showed a good linear distribution (r > or = 0.992 4). The average extraction recoveries were within 65.7%-94.2%. Intra-day RSD and inter-day RSD were less than 6% (n = 5). CONCLUSION This method seems to be quite specific, sensitive and accurate, and can be used to detect clozapine, olanzapine and mirtazapine in forensic and clinical analytic toxicology.
Benzodiazepines/blood* ; Chromatography, Liquid/methods* ; Clozapine/blood* ; Forensic Toxicology ; Humans ; Mianserin/blood* ; Mirtazapine ; Olanzapine ; Tandem Mass Spectrometry/methods*

Objectives : A diverse range of adverse effects has been linked to the application of antidepressants for the treatment of depressive disorder. Recently, evidence has been emerging of the adverse metabolic effects of antidepressants. This study investigated the effects of antidepressants on plasma glucose and other factors in the fat and muscle tissue relating to metabolism. METHODS : Long-Evans-Tokushima-Ostuka (LETO) rats were used to evaluate the effects of different antidepressants. Amitriptyline, fluoxetine, and mirtazapine were administered to each of three subgroups for 4 weeks, between 11 and 15 weeks old, while a fourth subgroup was administered no antidepressant during the same period. Changes of weight and daily intake were monitored. Tissues and blood were collected at 15 weeks. RESULTS : The fluoxetine subgroup showed lower weight gain and lower food efficacy ratio than did the other subgroups. Blood glucose and other circulating factors showed no significant differences among groups, except for the leptin levels of the fluoxetine subgroup. However, the amitriptyline and mirtazapine subgroups showed similar patterns in the response of mRNA expression of peroxisome proliferator-activated receptors gamma cofactor-1 and uncoupling protein-1, 2, 3. CONCLUSION : These results could indicate possible differences in metabolic response based on the kind of antidepressant used.
Amitriptyline ; Animals ; Antidepressive Agents ; Blood Glucose ; Depressive Disorder ; Energy Metabolism ; Fluoxetine ; Glucose ; Leptin ; Mianserin ; Muscles ; Peroxisome Proliferator-Activated Receptors ; Plasma ; Rats ; RNA, Messenger ; Weight Gain