Automated analysis of quetiapine and other antipsychotic drugs in human blood by high performance-liquid chromatography with column-switching and spectrophotometric detection

Sachse, J.; Köller, Johannes; Härtter, Sebastian; Hiemke, Christoph

doi:10.1016/j.jchromb.2005.11.032

Cited by 76 publications

(46 citation statements)

References 28 publications

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“…Plasma drug quantification Drug quantification was determined using HPLC (Alliance 2475; Waters, Milford, MA, USA) [13,14]. In brief, 4 µl of internal standard (100 µg/ml amoxapine) was added to 250 µl of rat plasma.…”

Section: Methodsmentioning

confidence: 99%

Atypical antipsychotic drugs induce derangements in glucose homeostasis by acutely increasing glucagon secretion and hepatic glucose output in the rat

et al. 2008

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Aims/hypothesis Use of the second-generation antipsychotic drugs (SGAs) results in the development of obesity and a type 2 diabetes-like syndrome. We hypothesised that, in addition to the insulin resistance associated with the obesity, the SGAs might have acute effects on glucose metabolism that could contribute to the derangements in glucose metabolism. Methods We investigated the effects of therapeutically relevant levels of three different antipsychotic medications (haloperidol, quetiapine and clozapine) on glucose tolerance, measures of insulin resistance and hepatic glucose production, and on insulin and glucagon secretion in rats.Results We found that these drugs induce impaired glucose tolerance in rats that is associated with increased insulin secretion (clozapine>quetiapine>haloperidol) but is independent of weight gain. However, Akt/protein kinase B activation is normal, and at these levels of drug there was no effect on insulin action in fat cells or soleus muscle, and no effect on insulin sensitivity as evaluated by insulin tolerance tests. We show that clozapine induces increased glucose levels following pyruvate and glycerol challenges, indicating an increase in hepatic glucose output (HGO). Increased HGO would in turn increase insulin release and would explain the apparent phenotype mimicking insulin resistance. We provide evidence that this effect could at least in part be mediated by a stimulation of glucagon secretion. Conclusions/interpretation Our findings indicate that SGAs can cause acute derangements in glucose metabolism that are not caused by a direct induction of insulin resistance but act via an increase in glucagon secretion and thus stimulation of hepatic glucose production.

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Section: Methodsmentioning

confidence: 99%

Atypical antipsychotic drugs induce derangements in glucose homeostasis by acutely increasing glucagon secretion and hepatic glucose output in the rat

et al. 2008

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“…Several methods have been already published for the determination of quetiapine in biological samples using LC [37][38][39][40][41] or GC methods [6,18,21,32,33,42,43]. The aim of this work was to investigate quetiapine-related lethal cases to assess the contribution of quetiapine to the cause of death.…”

Section: Discussionmentioning

confidence: 99%

A validated GC/MS method for the investigation of quetiapine-related deaths in Greece

Papoutsis¹,

Katselou²,

Nikolaou³

et al. 2017

Eur J Forensic Sci

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Objective: Quetiapine is an atypical antipsychotic drug that is used to treat the symptoms of schizophrenia and other psychiatric disorders. During the last years, quetiapine has also been associated with cases of misuse and abuse, and there are strong indications that it possesses an addictive potential. A suitable method is necessary for the toxicological investigation of such cases. Materials and Methods: A simple gas chromatographymass spectrometric method was developed, validated, and applied for the determination of quetiapine in biological fluids during the investigation of quetiapine-related cases. The sample preparation procedure includes solid-phase extraction and silylation using N-methyl-N-tert-butyldimethylsilyl-trifluoroacetamide with 1% tert-butyldimethylsilylchloride. Results: The limits of detection and quantification were 1.50 and 5.00 ng/mL, respectively. The calibration curves were linear up to 2000 ng/mL (R 2 ≥ 0.991) and absolute recovery higher than 81%. Accuracy (intra-and inter-day) was found to be between −11.1 and 12.4%, whereas the precision was found to be <13.3%. The validated method was successfully applied to post-mortem blood samples during the toxicological investigation of 50 quetiapine-related sudden and violent deaths. Quetiapine was determined at toxic levels (>1800 ng/mL) in eight cases and at lower concentrations (5.21-1430 ng/mL) in the other 42 cases. It is remarkable to be mentioned that in all 50 cases one or more drugs were detected along with quetiapine. Conclusions: Quetiapine has been detected with increasing frequency in post-mortem cases in Greece during the last 3 years. This is in accordance with the growing concerns worldwide about the misuse or abuse of the drug and its contribution to the cause of death of quetiapine-related lethal cases. Physicians should be alert about the toxicity of quetiapine, its possible misuse or abuse, and its synergy with other drugs, medicinal or not, especially in patients under multiple drug therapy or drug addicts.

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“…After clean-up, a six-port valve is switched to connect the clean-up column with the analytical column. Using column switching with an on-line sample clean-up may be even more advantageous, since it enables automated sample analysis for routing clinical samples (Weigmann et al, 2001;Sachse et al, 2003Sachse et al, , 2006Yasui-Furukori et al, 2004;Kollroser and Schober, 2002;Olesen and Poulsen, 1993). Weigmann et al (2001) used a cyanopropyl (CPS) coated column (10 μm; 10 × 2.0 mm i.d.)…”

Section: High-performance Liquid Chromatographymentioning

confidence: 99%

Bioanalytical methods for the determination of antipsychotic drugs

Zhang

Terry

Bartlett

2008

Biomedical Chromatography

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Antipsychotic drugs are popular for the treatment of schizophrenia and other psychoses. In general, antipsychotics are administered in oral doses of only a few milligrams per day and they are widely metabolized in the body. Therefore, the concentration of these drugs in plasma is very low (pg-ng/mL levels). In addition, therapeutic drug monitoring (TDM) of antipsychotic drugs has proven to be of notable value for determining poor compliance of patients and addressing the challenges associated with considerable genetic variability in their metabolism. Thus, in order to conduct pharmacology and toxicology studies and clinical TDM of antipsychotics, as well as address the challenges associated with polypharmacy and drug metabolism, highly sensitive, selective and accurate bioanalytical methods are essential. The most recent studies on the determination of antipsychotics will be reviewed, including separation techniques, sample pretreatment, detectors and validation.

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Automated analysis of quetiapine and other antipsychotic drugs in human blood by high performance-liquid chromatography with column-switching and spectrophotometric detection

Cited by 76 publications

References 28 publications

Atypical antipsychotic drugs induce derangements in glucose homeostasis by acutely increasing glucagon secretion and hepatic glucose output in the rat

Atypical antipsychotic drugs induce derangements in glucose homeostasis by acutely increasing glucagon secretion and hepatic glucose output in the rat

A validated GC/MS method for the investigation of quetiapine-related deaths in Greece

Bioanalytical methods for the determination of antipsychotic drugs

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