N-acetylcysteine interference of Trinder-based assays

• N-acetylcysteine (NAC) interference of Trinder-based assays has been reported.
• Serial dilutions of NAC were created to characterize this interference.
• Thresholds indicating 10% inhibition of Trinder-based assays by NAC were derived.
• Intravenous (IV) NAC is used for the treatment of acetaminophen (APAP) overdose.
• Minor inhibition of enzymatic creatinine (Cr) during such treatment was observed.

ObjectivesThe primary objective of this study was to evaluate potential interference of Trinder-based chemistry assays by N-acetylcysteine (NAC). A secondary objective was to look for evidence of interference in patients treated with NAC for acetaminophen (APAP) overdose.Design and methodsDilutions of NAC in plasma were tested for interference using the following Roche Diagnostics Trinder-based assays on a cobas 8000 system: enzymatic creatinine (Cr), cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), triglycerides (TRIG), and uric acid (UA). Two non-Trinder Roche assays — urea nitrogen (BUN) and glucose (GLUC) — were tested as controls. Sekisui N-geneous® low-density lipoprotein cholesterol (LDL-C) reagent was also evaluated. Retrospective chart review of APAP overdose cases over 49 months was conducted to look for differences in plasma Cr before and after intravenous (IV) NAC administration.ResultsNAC concentrations (shown in parentheses) that caused ≥ 10% inhibition for individual assays were (in order of sensitivity to interference): TRIG (570 mg/L) > CHOL (740 mg/L) ≈ Cr (790 mg/L) > UA (1100 mg/L) > HDL-C (1760 mg/L) > LDL-C (2900 mg/L). Neither BUN nor GLUC achieved significant inhibition up to 10,000 mg/L NAC. Evidence for relatively minor inhibition of Cr was observed in patients after NAC administration.ConclusionsNAC inhibition of the assays investigated typically occurs at concentrations higher than expected during IV and oral NAC therapy.