Simultaneous determination of cyclic antidepressants and their related drugs and the estimation of new metabolites in human whole blood and urine by MALDI-QTOF-mass spectrometry

Abstract

A rapid and sensitive method using matrix-assisted laser desorption ionization (MALDI)-quadrupole time-of-flight (QTOF)-mass spectrometry (MS) was developed for the analysis of six tricyclic antidepressants (ADs) and their related drugs, such as amitriptyline, carbamazepine, clomipramine, imipramine, nortriptyline, quetiapine, and two tetracyclic ADs, mianserin and mirtazapine, because these eight drugs are commonly observed medicines in poisoning cases in Japan. In the present MALDI-MS method, the limits of detection were 0.3-2 ng/ mL. The present method provided a simple and high throughput simultaneous analysis of these drugs. This is the first report dealing with quantitation of ADs and their related drugs in biological samples by MALDI-MS. In addition, we applied the MALDI-MS to two authentic cases, and three new metabolites of amitriptyline and three new metabolites of quetiapine could be detected in blood and urine samples in the two cases when regioisomers were counted as one metabolite.

Interpol review of controlled substances 2016–2019

“…Mianserin (a psychoactive tetracyclic antidepressant) : 2016 selective micro-electromembrane extractions (mu-EMEs) of the colored indicators metanil yellow and congo red (visual proof-of-principle) and the small drug substances nortriptyline, papaverine, mianserin, and citalopram(model analytes) based on their acid-base strength [ 306 ]; MALDI- QTOF- MS method for the analysis of six tricyclic antidepressants (ADs) and their related drugs, such as amitriptyline, carbamazepine, clomipramine, imipramine, nortriptyline, quetiapine, and two tetracyclic ADs, mianserin and mirtazapine, because these eight drugs are commonly observed medicines in poisoning cases in Japan [ 307 ]; 2017 chemometric evaluation of the combined effect of temperature, pressure, and co-solvent fractions on the chiral separation of basic pharmaceuticals (alprenolol, atenolol, metoprolol, propranolol, clenbuterol, and mianserin) using SFC [ 308 ]; development of hydrophilic interaction liquid chromatography-ESI/MS/MS method for the determination of olopatadine in tear matrix using Mianserin hydrochloride as an internal standard [ 309 ]; synthesis and characterization of tetrabutylammonium and tetramethylammonium amino acid salts (chiral anions: 1-leucine, 1-proline, 1-histidine) to investigate their effect on chiral separations of ondansetron, mianserin, and ofloxacin using CE [ 310 ].…”

A rapid screening method for the detection of benzodiazepine drugs in environmental samples by MALDI-TOF mass spectrometry

“…Their method was used for real samples and the LODs were as low as 0.3-2 ng/mL. 27 Nozawa et al (2015) developed a rapid and sensitive method for the determination of eight BDZs and two metabolites in blood using MALDI-TOF-MS. Alphacyano-4-hydroxy cinnamic acid was used as a matrix to provide BDZ ionization. The method was optimized and applied successfully for forensic purposes.…”