Kathryn Smith (Presenter)
ARUP Laboratories
Authorship: Kathryn Smith(1,2), Adam Barker (1,3), Frederick G. Strathmann (1,3)
(1) ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT (2) ARUP Laboratories, Salt Lake City, UT (3) Department of Pathology, University of Utah, Salt Lake City, UT
| Short Abstract Liquid Chromatography Time of Flight Mass Spectrometry (LC-TOF/MS) allows for the high-throughput detection of multiple drugs and non-targeted analysis making it a good choice as a primary screening tool. LC-TOF/MS was utilized here as a broad-spectrum screen to determine the drug involvement in cases of accidental or intentional overdoses. This comprehensive test includes a simple dilute and shoot method identifying the presence of 111 specific pharmaceutical compounds, illicit drugs and their metabolites in a patient’s urine. The investigation of the utility of reference mass infusion to monitor individual sample ion suppression will also be discussed. |
Long Abstract
Introduction: Liquid Chromatography Time of Flight Mass Spectrometry (LC-TOF/MS) allows for the high-throughput detection of multiple drugs and non-targeted analysis making it a good choice as a primary screening tool. LC-TOF/MS was utilized here as a broad-spectrum screen to determine the drug involvement in cases of accidental or intentional overdoses. This comprehensive test includes a simple dilute and shoot method identifying the presence of over 100 specific pharmaceutical compounds, illicit drugs and their metabolites in a patient’s urine.
Methods: A method using LC-TOF/MS to measure drugs of abuse in urine samples was developed and validated. The method was first optimized for 111 specific drugs in both positive and negative mode to analyze both basic and acidic drug compounds. The test is a semi-quantification assay with a one point calibration curve using the analyte cutoff concentrations as well as a 50%, 150% and negative (blank) controls. The individual peak area counts were normalized to one of the eleven deuterated internal standard spiked into each sample. The pretreatment of the urine samples included a simple dilute and shoot method prepared at a 1:20 dilution. The accuracy of the method was determined by reinjecting patient samples that have tested positive on different validated urine screens.
Results: The extracted chromatographs for the 104 compounds ionized in positive mode and the 7 compounds ionized in negative mode at their cut-off concentrations as well as their internal standards will be shown. Cut-off levels, imprecision, accuracy, carryover and ion suppression of the method will be presented. The challenges of using LC-TOF/MS for the detection of over 100 drug compounds will be discussed. The scoring method used for drug identification including retention time, mass error and isotope pattern will be reported. A qualitative agreement of the data from LC-TOF/MS and various validated urine screens will also be presented. Furthermore, the feasibility of extracting the reference mass chromatography to assess ion suppression will be discussed.
Results:
Conclusion: LC-TOF/MS provides a single platform for the screening of multiple drugs of abuse. The simple dilute and shoot method removes the need for multiple extraction steps and requires only µL amounts of patient urine. In addition, exploring the use of reference mass infusion as a mechanism to monitor sample by sample ion suppression will provide a convenient means to interpret ion suppression in the clinical laboratories. This comprehensive drug test has the potential for retrospective screening to extend beyond drugs which were not originally screened.
References & Acknowledgements:
| Description | Y/N | Source |
| Grants | no | |
| Salary | no | |
| Board Member | no | |
| Stock | no | |
| Expenses | no |
IP Royalty: no
| Planning to mention or discuss specific products or technology of the company(ies) listed above: | no |