A Simple, Rapid and Reliable Method to Determine Imipramine and Desipramine in Mouse Serum Using Ultra-High-Performance Liquid Chromatography–Quadrupole-Time-of-Flight Mass Spectrometry

Abstract

A rapid and sensitive ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometric (UHPLC-Q-TOF-MS) method was developed for quantification of imipramine, one of the most widely used tricyclic antidepressants, and desipramine, an active metabolite of imipramine, in mouse serum. The developed method included a simple protein precipitation with acetonitrile in 50 μL of serum and analyte separation on an Acquity UPLC BEH C18 column using a gradient elution of acetonitrile with 0.1% formic acid and 20 mM ammonium formate. As a result, the entire analysis time was <20 min including the sample preparation and the LC-MS analysis. The limit of quantification was 5.0 ng mL(-1) for both imipramine and desipramine, and calibration curves were linear over the concentration range of 5.0-1,000.0 and 5.0-250.0 ng mL(-1) for imipramine and desipramine, respectively. Intraday precisions at three levels were 2.2-3.6 and 1.7-4.2% for imipramine and desipramine, respectively, whereas interday precisions were 2.6-5.0 and 2.0-8.4% for imipramine and desipramine, respectively. Accuracy ranged between 93.6 and 106.6% for imipramine and 94.1 and 106.4% for desipramine. Absolute recovery was 96.0-97.6% for imipramine and 87.0-99.5% for desipramine. Finally, the described method was applied to mice administered with imipramine, demonstrating the suitability for quantification of imipramine and desipramine for therapeutic drug monitoring or bioequivalence studies.

Application of AP-MALDI Imaging Mass Microscope for the Rapid Mapping of Imipramine, Chloroquine, and Their Metabolites in the Kidney and Brain of Wild-Type Mice

“…MS 2 spectra of m/z 281.20 showed similar product ions from standard imipramine and imipramine-treated mice kidneys (Figure 2A-C). These are the characteristic product ions of imipramine [17]. Similar to imipramine, MS 2 spectra of m/z 320.19 showed identical product ions from standard chloroquine and chloroquine-treated mice kidneys (Figure 2A,D,E), hence assigned as chloroquine [18].…”

Pharmacokinetics in rat plasma and tissue distribution in mice of galangin determined by UHPLC–MS/MS

“…A rapid, simple, and convenient sample treatment method with acceptable recovery and matrix effects is needed for LC-MS/MS analysis [26][27][28][29][30]. We mixed plasma samples (100 μL) with 200 and 300 μL of acetonitrile, and the results showed that the recovery was acceptable (~84% and 95%) with both quantities, but matrix effects were not acceptable with 200 μL of acetonitrile (~105% and 115%) and were acceptable for 300 μL of acetonitrile (~94% and 103%).…”

G protein-coupled receptors in neurodegenerative diseases and psychiatric disorders

“…Imipramine and Desipramine are examples of tricyclic drugs for major depressive disorders, anxiety, and ADHD. 403 They have high affinities to 5-HT2C and 5-HT2A receptor subtypes. The pharmacological properties of Amitriptyline are similar to Imipramine.…”