CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Karen Titus
September 2016—This fall, Brigham and Women’s Hospital, Boston, is taking the mass spec leap.
A plucky PR person might be tempted to refer to it as MassSpec LEAP!™ but Stacy Melanson, MD, PhD, doesn’t have time for such nonsense. As the associate director of clinical laboratories and co-director of chemistry, Dr. Melanson has more important matters to attend to.
She and her colleagues are shifting from using a screening immunoassay for pain management drug testing to up-front definitive testing by LC tandem mass spectrometry.
The decision is based, in part, on following the numbers. Seventy to 80 percent of patients are positive for one of the six common opioids—morphine, codeine, hydromorphone, hydrocodone, oxycodone, and oxymorphone. “Which makes sense—those drugs are the ones that are commonly prescribed to manage chronic pain,” says Dr. Melanson.
“But it didn’t make sense to screen for something that 80 percent of the time will require confirmatory or definitive testing,” Dr. Melanson adds, also noting that the opiates immunoassays have problems with both false-negatives (particularly for oxycodone and oxymorphone) and false-positive results. “So we made the decision to go right to definitive testing when we brought the testing in-house six years ago.”
Second of three parts.
Last month: Painstaking process of drug monitoring
Dr. Melanson and her colleagues also go straight to definitive testing for six benzodiazepines: temazepam, oxazepam, nordiazepam, alpha-hydroxyalprazolam, 7-aminoclonazepam, and lorazepam. It was a decision made several years ago. “We used to screen with an immunoassay and only confirm the positives,” she says. “But we published a few papers that have shown there’s a high rate of false-negatives, particularly for the newer benzodiazepines that are being prescribed, lorazepam and clonazepam. Thirty, 40 percent of our patients were screening negative by immunoassay but were actually positive with detectable levels of benzodiazepines by mass spectrometry” (Darragh A, et al. Pain Physician. 2014;17:359–366; Snyder ML, et al. Pain Physician. 2016. In press). This fall, Brigham and Women’s Hospital plans to eliminate all immunoassay testing for pain management and switch to definitive testing by LC tandem mass spectrometry for all drugs in its pain management panel, including fentanyl, buprenorphine, methadone, and illicit substances.
Dr. Melanson
The limitations of immunoassays (see “Painstaking process of drug monitoring,” CAP TODAY, August 2016) may tilt other laboratories in the direction of mass spectrometry as well. “Confirmation testing is a vital part of pain management drug testing,” says Tai C. Kwong, PhD, professor of pathology and laboratory medicine and director of the hematology/chemistry laboratory, University of Rochester (NY) School of Medicine and Dentistry. Not only is mass spec useful in this regard, but it can be used directly, without initial screen by immunoassay, says Dr. Kwong.
A confirmation test should be based on an analytical principle that differs from that of the immunoreaction and be more specific than immunoassay (to eliminate false-positives) and of equal or greater sensitivity than immunoassay. Mass spectrometry hits the bull’s-eye for all three.
Mass spectrometry can confirm true positives and eliminate false-positives. The latter interferences are caused by drugs that are structurally unrelated to target drugs, such as ofloxacin and opiates assays, bupropion and amphetamines assays, and oxaprozin and benzodiazepines assays. Since assays from different manufacturers have different profiles of interfering substances, says Dr. Kwong, laboratories need to consult package inserts and technical support services.
A confirmatory test can also provide specific information about which drugs and metabolites are present, unlike the class immunoassays. This is important because a patient may have taken more than just the prescribed drug, says Dr. Kwong, who spoke about mass spectrometry with CAP TODAY as well as at an AACC virtual conference on drug monitoring for pain management. With an opiates immunoassay, he adds, the results will be the same regardless of the drug combination, whether morphine alone, morphine plus hydromorphone, or morphine plus hydrocodone plus hydromorphone. All would yield the same result: positive. “Without specific identification, you can appreciate how much important information is lost.”