title: Comparison of Different Time of Flight-Mass Spectrometry Modes for Small Molecule Quantitative Analysis.
abstract: Currently, the use of time of flight (TOF)-mass spectrometry (MS) in quantitative analysis of small molecules is rare. Recently, the quantitative performance of TOF mass analyzers has improved due to the advancements in TOF technology. We evaluated a Q-TOF-MS in different modes, i.e., Q-TOF-full scan (Q-TOF-FS), Q-TOF-enhanced-full scan (Q-TOF-En-FS), MS(E), Q-TOF-targeted (Q-TOF-TGT), Q-TOF-enhanced-targeted (Q-TOF-En-TGT), and compared their quantitative performance against a unit resolution LC-MS-MS (tandem quadrupole) platform. The five modes were investigated for sensitivity, linearity, signal-to-noise ratio, recovery and precision using 11-nor-9-carboxy-Δ(9)-tetrahydrocannabinol (THC-COOH) as a model compound in electrospray ionization (ESI) with negative polarity. Preliminary studies indicated that Q-TOF-FS mode was the least linear and precise; hence, it was eliminated from further investigation. Total imprecision in remaining four modes was <10%. The Q-TOF-En-FS and Q-TOF-En-TGT showed better signal intensity than their respective modes without enhancement. Overall, peak signal intensity was the highest in MS(E) mode, whereas the signal-to-noise ratio was the best in the Q-TOF-En-TGT mode. Relatively, MS(E) and Q-TOF-En-TGT modes were the best overall performers compared with the other modes. Both MS(E) and Q-TOF-En-TGT modes showed excellent precision (coefficient of variation <6%), patient correlation (r > 0.99) and linearity (range, 5-455 ng/mL) for THC-COOH analysis when compared with LC-MS-MS. We also investigated the performance of the same four modes using methamphetamine in positive ESI. Quantitative data obtained by Q-TOF-En-TGT and MS(E), using both positive and negative ESI, suggest that these modes performed better than the other modes. While unit resolution LC-MS-MS remains the optimal technique for quantification, our data showed that Q-TOF-MS can also be used to quantify small molecules in complex biological specimens.
authors.affiliation: Department of Pathology, Center for Advanced Laboratory Medicine, University of California, San Diego, San Diego, CA, USA.
authors.forename: Nandkishor S
authors.initials: NS
authors.lastname: Chindarkar
authors.affiliation: Department of Pathology, Center for Advanced Laboratory Medicine, University of California, San Diego, San Diego, CA, USA Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea nayadoo@hanmail.net.
authors.forename: Hyung-Doo
authors.initials: HD
authors.lastname: Park
authors.affiliation: Department of Pathology, Center for Advanced Laboratory Medicine, University of California, San Diego, San Diego, CA, USA.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Stone
authors.affiliation: Department of Pathology, Center for Advanced Laboratory Medicine, University of California, San Diego, San Diego, CA, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Fitzgerald
mesh_terms: D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000652:urine; D006801:Humans; D008694:Methamphetamine / Q000652:urine*; D015203:Reproducibility of Results; D059629:Signal-To-Noise Ratio; D013048:Specimen Handling; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D008694:Methamphetamine; C016780:11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid; D013759:Dronabinol