Abstract
A rapid and sensitive capillary zone electrophoresis (CZE) method with field enhanced sample injection (FESI) was developed and validated for the determination of quetiapine fumarate in beagle dog plasma, with a sample pretreatment by LLE in 96-well deep format plate. The optimum separation was carried out in an uncoated 31.2 cm × 75 μm fused-silica capillary with an applied voltage of 13 kV. The electrophoretic analysis was performed by 50 mM phosphate at pH 2.5. The detection wavelength was 210 nm. Under these optimized conditions, FESI with acetonitrile enhanced the sensitivity of quetiapine about 40–50 folds in total. The method was suitably validated with respect to stability, specificity, linearity, lower limit of quantitation, accuracy, precision and extraction recovery. Using mirtazapine as an internal standard (100 ng/mL), the response of quetiapine was linear over the range of 1–1000 ng/mL. The lower limit of quantification was 1 ng/mL. The intra- and inter-day precisions for the assay were within 4.8% and 12.7%, respectively. The method represents the first application of FESI-CZE to the analysis of quetiapine fumarate in beagle dog plasma after oral administration.
Highlights
Quetiapine fumarate (QTP), whose chemical name is bis[2-(2-[4-(dibenzo[b,f ][1,4]thiazepin11-yl)]ethoxy)ethanol]fumarate, Figure 1A, is a dibenzothiazepine derivative with an atypical neuropharmacological profile
Studies [1,2,3,4] have showed that quetiapine is very effective for negative and positive schizophrenia, as well as cognitive impairment, with slightly choline resistant and rarely granulocytopenia
capillary zone electrophoresis (CZE) method with electrokinetic injection in combine with dissolving the sample in 65% ACN yields provided a sensitivity enhancement of about 40–50 folds in comparison with the same sample dissolved in 10% buffer
Summary
Quetiapine fumarate (QTP), whose chemical name is bis[2-(2-[4-(dibenzo[b,f ][1,4]thiazepin11-yl)]ethoxy)ethanol]fumarate, Figure 1A, is a dibenzothiazepine derivative with an atypical neuropharmacological profile. Due to the highest serotonin/dopamine binding ratio, quetiapine makes the serotonin type 2 (5-HT2 )-receptor blocking effect about twice as strong as the dopamine D2 -receptor blocking effect. As a result of this binding pattern, the extrapyramidal side effects of quetiapine are minimal [3,5,6,7,8]. Those characteristics make quetiapine well tolerated and effective in patients who have Alzheimer’s disease or Parkinson’s disease [3,4]. Quetiapine is metabolized by the CYP450 system, primarily by CYP3A4 enzyme [5,9]
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