How do I interpret and use quantitative buprenorphine and norbuprenorphine urine levels?

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TABLE 1

Interpreting urinary buprenorphine and norbuprenorphine levels

	Total urinary buprenorphine (ng/mL)^a	Total urinary norbuprenorphine (ng/mL)^a	N:B ratio^b	Differential or likely diagnosis
Scenario 1	> 20	> 45	Usually > 0.26	Recent dosing of at least some buprenorphine
Scenario 2	Low, ≤ 20^c	Low, ≤ 45^c	Usually > 0.26	Regular recent dosing Dosing at low levels Use of a CYP3A4-inducer Increased time since last dose Dilute urine
Scenario 3	Positive, but low	Negative or very low	< 1 (may be 0)	Recent (within hours) dosing of buprenorphine for first time in days
Scenario 4	High, usually > 700	Negative	0	Buprenorphine spiking and no recent dosing
Scenario 5	High, usually > 700	Positive	< 0.26	Probable 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