Best practices for monitoring opioid compliance---making the case for using blood and liquid chromatography-tandem mass spectrometry for screen analysis.

摘要

Pain is the main reason people seek medical attention and it is estimated that approximately 100 million people in the United States suffer from chronic pain. The most commonly abused opioids, hydrocodone and oxycodone, are frequently prescribed to treat moderate and severe pain. According to Centers for Disease Control and Prevention, even though the population of the United States is less than 5% of the world's population, its population consumed approximately 80% of the world's supply of oxycodone and 99% of hydrocodone. Opioids carry high addiction liability and potential abuse. Opioid tolerance, due mainly to desensitization of opioid receptors, is followed by addiction and may sometimes fatal overdose. The addiction liability and potential for abuse of opioid drugs require close monitoring of the users of these prescribed medications. Abuse and diversion of opioids have resulted in a nationwide epidemic. The current practice for verifying compliance is predominantly by regular urine drug testing. Using immunoassay-based techniques which detect only classes of drugs, multiple assays must be run to detect different drugs in the urine sample. Chromatographic screening assays are becoming more common due to their ability to detect several drugs and their metabolites from a single specimen at clinically low concentrations. The aims of this project were to perform a literature review on (a) the current state of drug testing for patients in pain clinics with regard to urine, oral fluid and blood, (b) determine the value of the use of blood for compliance monitoring and (c) determine if the use of liquid chromatography-tandem mass spectrometry methodology would be a better testing strategy.;Urine drug testing is the predominant test performed to monitor compliance. More recent studies in which participants ingested 80 -- 240 mg doses of oxycodone on chronic basis show that one could not correlate reliably measure compliance using urine drug levels. Urine drug levels do not correlate with the patients' clinical symptoms and contain only drug metabolites. The ease of collection of oral fluid, which is similar to urine, is becoming increasingly popular as an alternative specimen. However, oral fluids contain predominantly the parent drug and detection varies with time of collection and several other factors. Attempts to relate oral fluid with blood drug levels (oral fluid: blood ratios) are ongoing but may be specific to each drug. Unlike urine and oral fluid, drug concentration in blood correlates with patients' clinical systems. Hydrocodone and oxycodone are the most prescribed opioids and blood levels in pain patients are typically 8-38 ng/mL and 20-50 ng/mL, respectively. The toxic blood levels are above 100 ng/mL and 200 ng/mL for hydrocodone and oxycodone, respectively. Thus, blood drug concentration can be used to monitor compliance to detect either toxic levels or therapeutic failure that may be due to individual cytochrome enzyme polymorphism and/or non-compliance. The ability to use the same blood specimen for pharmacogenomic testing as well as therapeutic drug monitoring makes it the best specimen. Parent drugs and metabolites are present in blood depending on the time of collection and provide valuable information for compliance monitoring. Pharmacogenetic testing, as part of personalized medicine, is currently expensive and is a major drawback. The results also showed that liquid chromatography-tandem mass spectrometry is gradually becoming a method of choice to replace immunoassays-based techniques. In a single run, it will allow the detection of several drugs, both prescribed (licit) or illicit. However, it is more costly, time-consuming and labor intensive.;In summary, the best specimen for analysis of drugs in patients prescribed with opioids is probably blood and the preferred methodology would be liquid chromatography-tandem mass spectrometry.