title: Therapeutic monitoring of benzodiazepines in the management of pain: current limitations of point of care immunoassays suggest testing by mass spectrometry to assure accuracy and improve patient safety.
abstract: BACKGROUND
  Concomitant use of opioids and benzodiazepines can result in significant untoward effects. Point of care (POC) urine testing devices are commonly used tools to monitor patient use of medications. These useful devices are relatively inexpensive and yield immediate results that can be acted upon at the time of the appointment, although numerous limitations have been identified for specific medications or medication classes. We established the diagnostic accuracy of a commonly used POC testing method for benzodiazepines.
  
  
  METHODS
  One thousand patients, from a single interventional pain practice receiving opioid therapy provided urine specimens as part of the usual practice of monitoring consistency with prescribed medications. These de-identified urine specimens were tested using LC-MS/MS and the results were compared using the standard calculations for sensitivity, specificity, and predicted value. Five specimens were excluded from the study because the prescribed flurazepam could not be confirmed by LC-MS/MS (the LC-MS/MS instrumentation was not set to identify flurazepam), resulting in 995 specimens.
  
  
  RESULTS
  Point of care assays yielded false negative results for patients prescribed benzodiazepines nearly 20% of the time (98 out of 498 patients). The point of care cup often failed to produce positive results for persons who were shown by LC-MS/MS to be taking lorazepam or clonazepam. Although only 26 out of 498 patients (5%) were prescribed ≥2 benzodiazepines, 73 out of 498 patients (15%) were found to be positive for that drug class.
  
  
  CONCLUSIONS
  POC immunoassay for benzodiazepines could fail to provide accurate information regarding patient specific medication use. The false positive and false negative rates of the immunoassay were particularly high for clonazepam and lorazepam. Further testing of patient specimens using more accurate methods such as LC-MS/MS is necessary to provide definitive data that can assist in clinical decision making, and potentially protect these patients from untoward effects, morbidity and mortality.
authors.affiliation: Millennium Laboratories, 16981 Via Tazon, San Diego, CA 92127, United States.
authors.forename: Charles
authors.initials: C
authors.lastname: Mikel
authors.forename: Amadeo J
authors.initials: AJ
authors.lastname: Pesce
authors.forename: Murray
authors.initials: M
authors.lastname: Rosenthal
authors.forename: Cameron
authors.initials: C
authors.lastname: West
mesh_terms: D001569:Benzodiazepines / Q000627:therapeutic use* / Q000652:urine*; D002853:Chromatography, Liquid / Q000379:methods*; D002998:Clonazepam / Q000627:therapeutic use / Q000652:urine; D005188:False Negative Reactions; D005189:False Positive Reactions; D006801:Humans; D007118:Immunoassay; D008140:Lorazepam / Q000627:therapeutic use / Q000652:urine; D013058:Mass Spectrometry / Q000379:methods*; D010147:Pain Measurement / Q000379:methods*; D061214:Patient Safety; D019095:Point-of-Care Systems; D012680:Sensitivity and Specificity
chemical_list: D001569:Benzodiazepines; D002998:Clonazepam; D008140:Lorazepam