Sensitivity and Specificity of Cocaine Metabolite Screening in View of the Analytical Performance of a Fluorescence Polarisation Immunoassay

Abstract

Immunoassays for drug screening are called 'qualitative' or 'semiquantitative' by the manufacturers of these tests and they urgently recommend the user to verify each result exceeding the recommended cut-off value by a confirmation test. For therapeutic drug monitoring assays or for the determination of tumour markers or hormones, similar recommendations are not given, although the same analytical technologies are used for these assays.A scientific validation of the commonly used cut-off values recommended by the official bodies (e. g. NIDA, DoD) is unfortunately not described in the accessible scientific literature.A solution to this problem was sought by evaluating the analytical characteristics of the assay and determining the diagnostic validity of the test using an immunoassay for the cocaine metabolite äs an example.Hundred urine samples frorn people suspected of cocaine abuse and 50 urine samples from patients unlikely to have consumed cocaine were analysed in triplicate with a commercially available fluorescence Polarisation immunoassay. From this data we assessed the analytical variance of the assay using the Computer program of Sadler & Smith (Clin. Chem. 36 (1990), 1346-1350). Using the functions provided, we calculated the limit of detection (LD) and the lower limit of quantification (LLQ) äs well äs the so-called power of defmition (PD) using a recently published method (Gautschi et a!., this Journal 31 (1993), 433-440). This procedure is mathematically well defmed, uses no artificial Standards or calibrators and is in compliance with IFCC recommendations.A clearly defined assessment of the diagnostic performance of an assay is of utmost importance for the discussion of adequate decision levels. The influence of different decision levels was demonstrated by assessing the diagnostic performance of the FPIA assay for benzoylecgonine by calculating the predictive values of a negative and positive test result for four different decision limits (12, 40, 150, recommended by DoD and 300 g/l, recommended by NIDA). The respeetive predictive values of the negative results were 0.931, 0.864, 0.704 and 0.661. The predictive value of a positive test result was uniformly 1.0 for all four cut-offs.These results are critically discussed wjth respect to the analytical performance of the assay, the socio-economic and legal consequences of the screening procedure.

A review of biological indicators of illicit drug use, practical considerations and clinical usefulness

“…Table 2 demonstrates the detection times for common psychoactive substances at cut-off concentrations encountered frequently in a laboratory setting. A scienti® c validation of the commonly used ª cut-offº values recommended by of® cial bodies is unfortunately not yet described in the accessible scienti® c literature (Hanseler & Keller, 1994).…”