Background: Liquid chromatography high-resolution mass spectrometry (LC-HRMS) with untargeted data collection is especially attractive for general unknown drug screening owing to its ability to identify unexpected compounds. LC-HRMS offers several advantages over traditional selected reaction monitoring (SRM) techniques and could be an ideal screening platform as long as its analytical performance is comparable to that of SRM-based methods.
Methods: We developed a broad-spectrum drug screen on a high-resolution mass spectrometer [tandem quadrupole time-of-flight (QqTOF)] that collected data in an untargeted manner and compared its performance to a nominal mass instrument [triple quadrupole linear ion trap (QqLIT)] that collected data in a targeted manner. Both methods used information-dependent acquisition of product ion spectra. We evaluated the lower limits of detection and matrix effects for each method and compared their ability to identify drugs in 100 routine clinical urine samples. Additional information (patient prescription history, drug screening results, etc.) was used to confirm discordant results.
Results: QqLIT was slightly more analytically sensitive than QqTOF; however, this difference did not significantly affect compound identification in patient samples. QqLIT identified 596 drugs in the urine samples, of which 531 (89%) were confirmed. QqTOF identified 515 drugs, of which 500 (97%) were confirmed. There were 562 instances of a confirmed drug (68 unique drugs) in the 100 urine samples; the methods were concordant in 469 of these instances.
Conclusions: Overall, QqTOF performed similarly to QqLIT and could serve as an alternative method for general unknown screening.
© 2015 American Association for Clinical Chemistry.