Evaluation of optimal urine screening and confirmation cut-off values for opiates, at a national reference laboratory

Objectives: To obtain optimal immunoassay screening and LC-MS/MS confirmation cut-offs for opiate group tests to reduce false positive (FP) and false negative (FN) rates. Methods: A total of 126 urine samples, -50 opiate screening negative, 76 positive according to the threshold of 300 ng/mL by CEDIA method - were confirmed by a full-validated in-house LC-MS/MS method. Sensitivity, specificity, FP, and FN rates were determined at cut-off concentrations of both 300 and 2,000 ng/mL formorphine and codeine, and 10 ng/mLfor heroinmetabolite 6-mono-acetyl-morphine (6-MAM). Results: All CEDIA opiate negative urine samples were negative for morphine, codeine and 6-MAM. Although sensitivity was 100% for each cut-off; specificity was 54.9% at CEDIA cut-off 300 ng/mL vs. LC-MS/MS cut-off 300 ng/mL and, 75% at CEDIA cut-off 2,000 ng/mL vs. LC-MS/MS cut-off 2,000 ng/mL. False positive rate was highest (45.1%) at CEDIA cut-off 300 ng/mL. At CEDIA cut-off 2,000 ng/mL vs. LC-MS/MS cut-off 300 ng/mL, specificity increased to 82.4% and FP rate decreased to 17.6%. All 6-MAM positive samples had CEDIA concentration >= 2,000 ng/mL. Conclusions: 2,000 ng/mL for screening and 300 ng/mL for confirmation cut-offs are the most efficient thresholds for the lowest rate of FP opiate results.