title: Signal enhancement of glucuronide conjugates in LC-MS/MS by derivatization with the phosphonium propylamine cation tris(trimethoxyphenyl) phosphonium propylamine, for forensic purposes.
abstract: Although chemical derivatization for signal enhancement in drug testing is most often associated with gas chromatography, it also has the potential to improve the detection of analytes poorly ionized by atmospheric pressure ionization techniques, such as electrospray ionization used in liquid chromatography-mass spectrometry. A number of acidic compounds, namely drug glucuronides (e.g. conjugates of temazepam, oxazepam, lorazepam, morphine, testosterone, epitestosterone, 5-α-dihydrotestosterone, androsterone, p-nitrophenol, and paracetamol) were successfully derivatized with tris(trimethoxyphenyl) phosphoniumpropylamine to introduce a quaternary cation functionality to the analytes. Benzodiazepine glucuronides were more specifically investigated, and following positive mode electrospray ionization mass spectrometry, average improvements to peak areas as a result of derivatization were 67-, 6-, and 7- fold for temazepam, oxazepam, and lorazepam glucuronides. Average improvements to the signal-to-noise ratios for temazepam, oxazepam, and lorazepam glucuronides were 1336-, 371- and 217-fold, respectively. The values obtained for the derivatized conjugate were also typically higher than those for the underivatized parent drug. Urine containing benzodiazepine glucuronides was also successfully derivatized. The data indicates potential for the use of charge derivatization to improve the detection of molecules with acidic functionalities by liquid chromatography-mass spectrometry (LC-MS) techniques in certain scenarios.
authors.affiliation: Analytical and Environmental Sciences Division, King's College London, London, UK.
authors.forename: Sophie C
authors.initials: SC
authors.lastname: Turfus
authors.forename: John M
authors.initials: JM
authors.lastname: Halket
authors.forename: Mark C
authors.initials: MC
authors.lastname: Parkin
authors.forename: David A
authors.initials: DA
authors.lastname: Cowan
authors.forename: Robin A
authors.initials: RA
authors.lastname: Braithwaite
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Kicman
mesh_terms: D001569:Benzodiazepines / Q000737:chemistry / Q000378:metabolism / Q000652:urine; D002853:Chromatography, Liquid; D044707:Forensic Sciences / Q000379:methods*; D020719:Glucuronides / Q000737:chemistry* / Q000652:urine; D006801:Humans; D009943:Organophosphorus Compounds / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism / Q000652:urine*; D011437:Propylamines / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D020719:Glucuronides; D009943:Organophosphorus Compounds; D004364:Pharmaceutical Preparations; D011437:Propylamines; C405845:tris(trimethoxyphenyl)phosphonium acetyl; D001569:Benzodiazepines
keywords: LC-MS/MS; derivatization; ionization; tris(trimethoxyphenyl) phosphonium propylamine (TMPP-C3H6NH2)