title: 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.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Yujin
authors.initials: Y
authors.lastname: Shin
authors.affiliation: Gachon Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon University, Incheon 21936, Republic of Korea.
authors.forename: Kwang-Hoon
authors.initials: KH
authors.lastname: Chun
authors.affiliation: College of Pharmacy, Duksung Women's University, Seoul 01369, Republic of Korea.
authors.forename: Hye-Ran
authors.initials: HR
authors.lastname: Yoon
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea jlee0610@skku.edu.
authors.forename: Jeongmi
authors.initials: J
authors.lastname: Lee
mesh_terms: D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003891:Desipramine / Q000097:blood*; D007099:Imipramine / Q000097:blood*; D057230:Limit of Detection; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D051379:Mice; D008813:Mice, Inbred ICR; D015203:Reproducibility of Results
chemical_list: D000929:Antidepressive Agents, Tricyclic; D007099:Imipramine; D003891:Desipramine