Pericardial fluid can provide preliminary drug-screening information when urine is unavailable, but it is not automatically interchangeable with urine. A 66-autopsy study documented benzodiazepine false-negatives in both matrices, including samples containing substantial parent-drug or metabolite concentrations. An automated positive-or-negative printout remained a presumptive result.
What the comparison included
Tominaga, Michiue and Maeda compared Triage-TOX, Triage-DOA and Monitect-9 using 51 urine specimens and 19 pericardial-fluid specimens from 66 forensic autopsies. Seventy specimens did not represent seventy independent deaths. Cases were selected from January 2011 through August 2014 to include a range of instrumentally detected drugs.
The bodies had no evident putrefactive changes. Samples were stored at −20°C until use. The investigators applied manufacturers’ urine-testing procedures to pericardial fluid as well. That experimental application should not be mistaken for proof that urine thresholds have identical diagnostic meaning in another matrix.
The selection included 24 urine and 13 pericardial-fluid specimens containing benzodiazepines or related compounds by instrumental analysis. These totals are different from the smaller subsets used in threshold-based comparisons. Parent drugs, metabolites and assay cross-reactivity all affected whether a screening device responded.
Automation did not eliminate false-negatives
Triage-TOX used an automated fluorescence-immunoassay reader to produce objective results without relying on a person’s interpretation of a faint visual signal. That improved objectivity did not guarantee detection.
The paper describes four benzodiazepine false-negative urine results with Triage-TOX, including specimens containing temazepam at 0.687 µg/mL, flunitrazepam at 0.738 µg/mL, lorazepam at 1.07 µg/mL and nordiazepam at 9.079 µg/mL. In pericardial fluid, reported Triage-TOX false-negative examples contained etizolam at 1.239 µg/mL and nordiazepam at 1.399 µg/mL.
These are specimen-specific drug or metabolite concentrations measured instrumentally. They are not interchangeable with an immunoassay’s class-calibrator concentration, and they do not identify a blood concentration or degree of sedation.
Why a second screen still was not confirmation
Monitect-9 detected benzodiazepines more readily in this selected material, but also produced more results the authors classified as false-positives. Some apparent disagreements required LC–MS/MS because low concentrations or metabolites were not detected by GC–MS. The comparison therefore depended on the reference procedure’s capabilities as well as the screening device.
The authors proposed that combining devices could help reduce misinterpretation. Agreement between two immunoassays, however, is not the same as analyte-specific instrumental identification and quantitation. Both screens can be influenced by their target coverage and cross-reactivity.
Instrumental testing used GC–MS and LC–MS/MS. The reported GC–MS detection thresholds for benzodiazepines and metabolites were 0.01–0.05 µg/mL, compared with 0.001–0.005 µg/mL for LC–MS/MS. The lower thresholds helped investigate discordant findings; they were not universal exposure or impairment cutoffs.
What the study did not validate
The small, deliberately selected specimen set does not establish predictive values for all autopsies. In particular, it did not validate performance in advanced decomposition. The authors also described problems with turbid deteriorating specimens, but those observations did not constitute a systematic decomposition experiment.
Several drug classes had no instrumentally positive specimens, so negative results for those classes could not demonstrate sensitivity. Nor did the study test whether a screening result alone correctly identified the cause of death. The device supplier partly supported the investigation, as disclosed by the authors.
Reviewers should retain the exact matrix, device, target compound, metabolite findings and follow-up method. For a related limitation of instrumental reporting, see why an unquantifiable result is not a negative test.
Primary source
Tominaga M, Michiue T, Maeda H. Evaluation of the on-site immunoassay drug-screening device Triage-TOX in routine forensic autopsy. Legal Medicine. 2015;17(6):499–502. doi:10.1016/j.legalmed.2015.10.007.
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