Anomalous urine drug testing results in Maltese heroin addicts

Abstract

The main aim in a urine drug testing programme for opiates is to detect and confirm heroin intake. The prevalence of atypical samples present amongst urine specimens obtained from the local population of patients undergoing methadone maintenance treatment (DETOX) was studied. For the purpose of this project, atypical samples would yield a negative total opiate immunoassay screen (cut-off 300 µg/L) and a positive 6-monoacetylmorphine (6 MAM) immunoassay screen (cut-off 1 0 µg/L). The strategy of utilizing the total opiate screen as the sole analytical tool may result in a number of individuals escaping detection. This phenomenon which was never studied locally cannot be satisfactorily explained with the current understanding of heroin metabolism. Possible xenobiotic inhibition in the heroin metabolic pathway and also the presence of enzymatic defects caused by known single-nucleotide polymorphism (SNP's) mutations were investigated. The results of the commercial 6 MAM immunoassay (CEDIA®) were compared with an HPLC and a GC-MS method to confirm authenticity and also assess the sensitivity of the assay. This study showed that 1.23% of the negative results issued for total opiates (cut-off 300 µg/L) are actually 'pseudo false negative'. Such results are analytically correct but might not be reflecting the actual patient situation. There seems to be no xenobiotic interactions with the heroin metabolic pathway, and the association with the presence of known SNP's was also excluded in 28.6% of the cases. By exclusion, it seems that urine collection timing in relation to heroin intake and to a much lesser extent heroin contamination of the urine sample are the most likely explanations for this phenomenon. With regards to the 6 MAM immunoassay kit currently being utilized at the Maltese Toxicology Lab (Mater Dei Hospital), the results indicate that it possesses excellent sensitivity since all preliminary positive 6 MAM results were confirmed by HPLC and GC-MS techniques. An additional 6 MAM immunoassay screen is not being recommended in cases of routine drugs of abuse screening since the prevalence of atypical samples may not be high enough to justify the additional expense. However it might be useful in cases of suspected opioid overdose that turn out to be total opiates negative.