Hydromorphone and codeine concentrations in oral fluid specimens from patients receiving substitution therapy with Substitol™ (morphine sulfate)

Abstract

This study aimed to determine whether hydromorphone and codeine can be detected in oral fluid specimens following administration of Substitol™, a slow‐release formulation of morphine. This is of interest for those monitoring treatment compliance using drug testing. Oral fluid specimens collected for compliance assessment in routine clinical practice or as part of a clinical trial were subjected to quantitative analysis of hydromorphone, morphine, codeine, and 6‐acetylmorphine using highly sensitive mass spectrometric methods. Oral fluid was collected using a Greiner Bio‐One saliva collection system. Patients undergoing substitution treatment with Substitol™, methadone, or buprenorphine were included, together with patients undergoing pain treatment with hydromorphone. Hydromorphone was detected in 642 of the 663 (97%) samples from substitol‐treated patients. Concentrations were not higher in methadone‐ and buprenorphine‐treated patients who relapsed into heroin use, or in patients on hydromorphone therapy. Codeine was detected in 29% of the samples. These concentrations were lower than those in patients who had relapsed to heroin use. Clinical administration of morphine can lead to detectable concentrations of both hydromorphone and codeine in oral fluids. This should be taken into consideration when using drug testing in oral fluid samples for compliance assessment in this patient group.

Sample Matrices for Mass Spectrometry–Based Adherence Monitoring: A Systematic Critical Review

“…There was a statistically significant relation between the OF and serum concentrations for most studied substances. Lierheimer et al 43 developed a method for the quantification of opioids in OF to differentiate between treatment adherence and misuse of opioids. For example, a concentration above 20 ng/mL of codeine in OF might indicate a second source of codeine in addition to the substitution therapy with morphine sulfate.…”

Towards adherence monitoring using breath or oral fluid as a matrix in a methadone maintenance treatment program for patients with a chronic heroin use disorder: Issues and interpretation of the results

“…Hence, the use of oral fluid and exhaled breath for adherence monitoring in clinical practice complicates the interpretation of the data regarding acetylcodeine as an unequivocal marker of illicit heroin use. The recent publication of a similar case by Lierheimer et al (24) demonstrates that the interpretation of screening results in patients using a slow-release formulation of morphine (Substitol TM ) as a substitution treatment, which contains up to 0.1% w/w codeine and is detectable in oral fluid, is also challenging.…”