TABLE 1

Interpreting urinary buprenorphine and norbuprenorphine levels

Total urinary buprenorphine (ng/mL)aTotal urinary norbuprenorphine (ng/mL)aN:B ratiobDifferential or likely diagnosis
Scenario 1> 20> 45Usually
> 0.26
Recent dosing of at least some buprenorphine
Scenario 2Low, ≤ 20cLow, ≤ 45cUsually
> 0.26
Regular recent dosing
Dosing at low levels
Use of a CYP3A4-inducer
Increased time since last dose
Dilute urine
Scenario 3Positive, but lowNegative or very low< 1 (may be 0)Recent (within hours) dosing of buprenorphine for first time in days
Scenario 4High, usually > 700Negative0Buprenorphine spiking and no recent dosing
Scenario 5High, usually > 700Positive< 0.26Probable buprenorphine spiking, likely recent dosing if norbuprenorphine level is not low
Possible regular dosing when N:B ratio > 0.02 but < 0.26
  • a Total urinary levels listed here include the parent compound and the glucoronidated form (eg, total buprenorphine = free buprenorphine + buprenorphine- 3-glucoronide) achieved after laboratory hydrolysis.

  • b Some studies suggest using an N:B ratio of 0.02 as a threshold for identifying urine spiked with unconsumed buprenorphine. Using a more sensitive threshold of 0.26 keeps a broader differential.

  • c Some studies consider values < 100 ng/mL to be low.

  • CYP3A4 = hepatic cytochrome P450 3A4; N:B ratio = ratio of norbuprenorphine to buprenorphine