Buprenorphine, a Schedule III – V (depending on the formulation) narcotic,is a semi-synthetic opiate derived from thebaine and is part of the phenanthrenes group1. This drug is an analgesic with mixed agonist-antagonist properties that is 20-40 times more potent than morphine and is utilized as a treatment for opioid dependence1,2. It is prescribed under the following trade names: Bunavail, Buprenex, Butrans, Suboxone, and Zubsolv. Buprenorphine is highly prescribed throughout the United States with 9.3 million being dispensed in 2012 and 2.5 million in the first quarter of 20133.
Buprenorphine is administered orally via a buccal film and a sublingual film/tablet with dosage ranges of 2.1-6.3 or 0.5-12 mg, respectively. It is also available in an extended release formulation via a transdermal patch with a dose of 5-20 µg/hr and a parenteral injection is obtainable with a usual dose of 0.3 mg. Naloxone is commonly combined with buprenorphine in order to minimize abuse potential2.
Following a 2 mg sublingual dose, the average peak plasma concentration occurred at 1.3 hrs with a half-life of 18-49 hrs. A 0.3 mg intravenous dose resulted in an average peak plasma concentration at 2 minutes with a half-life of 2-4 hrs2. The bioavailability is approximately 51% via sublingual administration or 28% via a buccal film5.
Buprenorphine is primarily N-dealkylated by CYP3A4 in order to form the pharmacology active norbuprenorphine in which both undergo conjugation2.
Within 6-11 days, approximately 95% of a dose is eliminated with around 68% excreted in the feces and 27% in the urine. In urine, the majority of the drug is excreted as buprenorphine glucuronide and norbuprenorphine glucuronide at 9.4% and 11%, respectively2,4.
A highly specific buprenorphine Enzyme Immunoassay (EIA) screening methodology is utilized for the detection of buprenorphine and norbuprenorphine with a cutoff concentration of 5 ng/mL. Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) is used to confirm and quantify buprenorphine and norbuprenorphine, with a cutoff concentration of 3 ng/mL and 10 ng/mL, respectively. The urine samples are hydrolyzed prior to analysis and total buprenorphine and norbuprenorphine concentrations are reported.
Patients prescribed buprenorphine should contain both buprenorphine and norbuprenorphine in the urine. In a study conducted by McMillen et al., out of 1,946 positive buprenorphine samples, 94.45% contained buprenorphine and norbuprenorphine, 4.87% had only norbuprenorphine present, and 0.67% contained only parent drug6. If buprenorphine is in high concentrations in the urine without the presence of norbuprenorphine, the possibility of patient tampering should be considered; however, patients co-administered CYP3A4 inhibitors may have lower than expected concentrations of norbuprenorphine.