title: A comparative solid-phase extraction study for the simultaneous determination of fluvoxamine, mianserin, doxepin, citalopram, paroxetine, and etoperidone in whole blood by capillary gas-liquid chromatography with nitrogen-phosphorus detection.
abstract: This paper reports a simple and reliable gas chromatographic method with nitrogen-phosphorus detection without derivatization for the simultaneous detection of fluvoxamine, mianserin, doxepin, citalopram, paroxetine, and etoperidone in whole blood as part of a systematic toxicological analysis (STA). All drugs were studied at concentration levels of 100-2000 ng/mL, except paroxetine for which it was necessary to study at concentration levels of 400-8000 ng/mL. A comparative and validation study using two solid-phase extraction (SPE) columns, Chem Elut and Bond Elut Certify, was developed regarding their recovery, precision, sensitivity, and matrix purification efficiency. The Chem Elut columns, diatomaceous earth, are closely related to conventional liquid-liquid extraction. The Bond Elut Certify columns, more recently developed in the market, are mixed SPE (reversed-phase and cation exchange sorbent). Recoveries for the antidepressants using Chem Elut columns at 500 ng/mL (2000 ng/mL for paroxetine) were in the range 43-72% with intra- and interassay precisions of less than 10% and 16%, respectively. Limits of detection (LODs) and quantitation (LOQs) for fluvoxamine, mianserin, doxepin, citalopram, and etoperidone ranged from 18 to 236 ng/mL and 60 to 786 ng/mL, respectively. LOD and LOQ for paroxetine were 303 and 1009 ng/mL, respectively. Recoveries of these compounds using Bond Elut Certify columns at 500 ng/mL (2000 ng/mL for paroxetine) were in the range 52-83% with intra- and interassay precisions of less than 6% and 8%, respectively. LODs and LOQs for fluvoxamine, mianserin, doxepin, citalopram, and etoperidone ranged from 7 to 28 ng/mL and 23 to 93 ng/mL, respectively. LOD and LOQ for paroxetine were 113 and 376 ng/mL, respectively. An excellent linearity was observed with both procedures from the LOQs up to the upper studied concentration level. In general, higher recoveries, cleaner extracts, better sensitivity, better precision, and reduced solvent consumption and disposal were achieved for the screening of these antidepressants with the use of the mixed SPE Bond Elut Certify compared with Chem Elut columns. The application of these methods on a forensic case study is also presented.
authors.affiliation: Department of Chemistry, National Institute of Toxicology, Ministry of Justice. C/Luis Cabrera 9, 28002 Madrid, Spain. mariantmart@terra.es
authors.forename: María A
authors.initials: MA
authors.lastname: Martínez
authors.forename: Carolina
authors.initials: C
authors.lastname: Sánchez de la Torre
authors.forename: Elena
authors.initials: E
authors.lastname: Almarza
mesh_terms: D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000097:blood*; D000929:Antidepressive Agents, Tricyclic / Q000097:blood*; D002849:Chromatography, Gas / Q000295:instrumentation / Q000379:methods*; D002853:Chromatography, Liquid / Q000295:instrumentation / Q000379:methods*; D015283:Citalopram / Q000097:blood; D004316:Doxepin / Q000097:blood; D005260:Female; D016666:Fluvoxamine / Q000097:blood; D006801:Humans; D008803:Mianserin / Q000097:blood; D009584:Nitrogen; D017374:Paroxetine / Q000097:blood; D010758:Phosphorus; D015203:Reproducibility of Results; D014196:Trazodone / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D015283:Citalopram; D004316:Doxepin; D008803:Mianserin; D010758:Phosphorus; D017374:Paroxetine; C013528:etoperidone; D009584:Nitrogen; D016666:Fluvoxamine; D014196:Trazodone