Emily Ryan (Presenter)
LabSource, LLC
Authorship: Emily L Ryan (1), Alicia Darragh (1), Lindsey Contella (1)
(1) LabSource, LLC
| Short Abstract Our objective was to assess the differences in detection rates in a diverse population for the screen and confirm paradigm versus direct to definitive testing for urine toxicology testing. 4794 urine specimens were qualitatively screened for the presence 17 different drug or drug classes on the Olympus AU680 analyzer (Beckman Coulter, Inc., Brea, CA). All samples were then quantitatively tested on an LC-MS/MS platform (Sciex, Framingham, MA or Agilent Technologies, Santa Clara, CA) for the free and conjugated forms of 74 analytes. Data were reviewed to determine what positive specimens would have been missed if only screened positive results were reflexed for LC-MS/MS testing. With the current complexity of pharmaceuticals immunoassay testing missed a compound in 44% of the specimens. Mass spectrometry methods are essential to obtain an accurate results for treatment decisions. |
Long Abstract
Historically, clinical laboratorians have been concerned with false positive rates in urine toxicology testing, but missed positives or false negatives may be more clinically relevant in many populations. Today in addiction and pain management patients, the complexity of pharmaceuticals cannot be easily covered by immunoassay screening. Our objective was to assess the differences in detection rates in multiple patient populations between the traditional paradigm of screen and confirm and direct to definitive testing.
A total of 4794 urine specimens were qualitatively screened for the presence 17 different drug or drug classes on the Olympus AU680 analyzer (Beckman Coulter, Inc., Brea, CA). Homogenous enzyme immunoassays were used with a one point calibration at the decision point. All samples were then quantitatively tested on an LC-MS/MS platform (Sciex, Framingham, MA or Agilent Technologies, Santa Clara, CA) for the free and conjugated forms of 74 analytes. Specimen were prepared under enzymatic hydrolysis with glusulase® (Perkin Elmer, Waltham, MA) and analyzed against a 4 point calibration curve. Any results above the detection limit for that analyte were considered positive.
Data from 3 sites (two addiction and one pain management) were reviewed to determine what positive specimens would have been missed if definitive testing was done only immunoassay screened positive specimens. Of the 4794 specimens reviewed 1646 (34%) had analytes not covered by immunoassay testing, 662 (14%) specimens were negative in the immunoassay screen but the testing analyte was present at detectable levels, and 351 (7%) specimens were positive on screen but confirmed negative. The most common false negatives were benzodiazepines (344), opiates (165), and cocaine metabolite (81) assays.
The more clinically relevant question is: “how many positive patients would have been missed with the traditional paradigm?” 39% of patients taking benzodiazepines were false negative due to the metabolites of commonly prescribed medications (7-aminoclozaepam and lorazepam) not cross-reacting well in the immunoassay. Opiates, a much more commonly used (and abused) drug class, showed only an 15% false negative rate. Interestingly, more than a quarter (36%) of benzoylecgonine positive specimens were missed on screen.
Of the common medications not covered by the screening panel the most common were the anticonvulsants pregabalin and gabapentin and the synthetic opioids naltrexone, tramadol and fentanyl. While there are FDA approved assays for some of these, they are not widely used, leading clinicians to make decisions based upon incomplete results. In these specimens approximately half (47%) of the toxicology results would be incomplete or wrong if it were based on traditional urine testing paradigms.
From this data it becomes clear in populations where it is necessary to have a clear picture of medication and illicit use the traditional paradigm of screen and confirm is not sufficient to meet medical necessity. This data demonstrates that the currently available FDA-approved methods for urine drug screening are not sufficient to meet the need of the physician. The most common benzodiazepine used in addiction medicine, clonazepam, cannot be confirmed using traditional benzodiazepine immunoassays. Mass spectrometry methods are essential to obtain an accurate picture in these patients for treatment decisions.
References & Acknowledgements:
| Description | Y/N | Source |
| Grants | no | |
| Salary | yes | LabSource, LLC |
| 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: | yes |