A rapid LC-MS/MS method for simultaneous determination of quetiapine and duloxetine in rat plasma and its application to pharmacokinetic interaction study

Abstract

Combinations of new antidepressants like duloxetine and second-generation antipsychotics like quetiapine are used in clinical treatment of major depressive disorder, as well as in forensic toxicology scenarios. The drug–drug interaction (DDI) between quetiapine and duloxetine is worthy of attention to avoid unnecessary adverse effects. However, no pharmacokinetic DDI studies of quetiapine and duloxetine have been reported. In the present study, a rapid and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for simultaneous determination of quetiapine and duloxetine in rat plasma. A one-step protein precipitation with acetonitrile was applied for sample preparation. The analytes were eluted on an Eclipse XDB-C 18 column using the mixture of acetonitrile and 2 mM ammonium formate containing 0.1% formic acid at a gradient elution within 6.0 min. Quantification was performed in multiple-reaction-monitoring mode with the ion transitions m/z 384.4 → 253.2 for quetiapine, m/z 298.1→154.1 for duloxetine and m/z 376.2→165.2 for IS (haloperidol), respectively. Good linearity was obtained in the range of 0.50–100 ng/mL for quetiapine (r 2 = 0.9972) and 1.00–200 ng/mL for duloxetine (r 2 = 0.9982) using 50 μL of rat plasma, respectively. The method was fully validated with accuracy, precision, matrix effects, recovery and stability. The validated data have met the acceptance criteria in FDA guideline. The method was applied to a pharmacokinetic interaction study and the results indicated that quetiapine had significant effect on the enhanced plasma exposure of duloxetine in rats under combination use. This study could be readily applied in therapeutic drug monitoring of major depressive disorder patients receiving such drug combinations.

Development of determination methods of quetiapine fumarate for forensic-pharmaceutical purposes

“…Typically, the GC-MS method provided high sensitivity and accuracy, but according to the literature, all previous studies used time-consuming sample preparation, such as derivatization of the sample before determination, without determining the minimum concentration of quetiapine that can be determined under these conditions [28]. The proposed and used GC-MS method is characterized by relatively simple sample preparation, relatively short analysis time, the ability to detect the substance without the use of standard samples, due to the presence of large electronic libraries of mass spectra.…”

Achiral and chiral analysis of duloxetine by chromatographic and electrophoretic methods, a review on the separation methodologies

“…An Xterra RP8 column (50 × 4.6 mm, 5 μm) and an isocratic mobile phase consisting of 30 mM ammonium formate (pH 5.0) and acetonitrile were used in the separation. The LLOD and LLOQ were 0.04 and 0.1 ng mL −1 , respectively (Reddy et al, 2012 (Chen et al, 2019).…”

“…The triple quadrupole MS was operated in positive ion ESI mode, and a multiple reaction monitoring mode was applied for the quantification. Pharmacokinetic interaction of quetiapine and duloxetine was studied; it was found that concomitant administration of both substances significantly increased plasma concentrations of DLX (Chen et al, 2019).…”

Recent advances in liquid chromatographic methods for the determination of selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors

“…A good balance between simplicity and sensitivity for duloxetine determination was achieved by Chen et al (). Duloxetine rat plasma samples were treated by a one‐step protein precipitation method without drying or redissolving, thus greatly simplifying the sample preparation process.…”