Comparison of different time of flight-mass spectrometry modes for small molecule quantitative analysis

  • Nandkishor S. Chindarkar
  • , Hyung Doo Park
  • , Judith A. Stone
  • , Robert L. Fitzgerald

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

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), MSE, Q-TOF-targeted (Q-TOF-TGT), Q-TOF-enhancedtargeted (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-tonoise ratio, recovery and precision using 11-nor-9-carboxy-D9-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 MSE mode, whereas the signal-to-noise ratio was the best in the Q-TOF-En-TGT mode. Relatively, MSE and Q-TOF-En-TGT modes were the best overall performers compared with the other modes. Both MSE and Q-TOF-En- TGT modes showed excellent precision (coefficient of variation <6%), patient correlation (r > 0.99) and linearity (range, 52455 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 MSE, 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.

Original languageEnglish
Pages (from-to)675-685
Number of pages11
JournalJournal of Analytical Toxicology
Volume39
Issue number9
DOIs
StatePublished - Nov 2015
Externally publishedYes

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