Buprenorphine and norbuprenorphine concentrations in human breast milk samples determined by liquid chromatography-tandem mass spectrometry

Abstract: Buprenorphine (BUP) is considered to be safe during pregnancy. However, the extent of BUP transfer into breast milk has not been thoroughly investigated. Since the drug concentration in the milk is one of the determinants in the assessment of the exposure risk, a rapid and sensitive LC-MS/MS method has been developed and evaluated to measure BUP and norbuprenorphine (norBUP) concentrations in milk. Recovery of the analytes by a solid phase and 2 liquid-liquid extraction procedures has been compared. The lower limits of detection and quantification were 0.05 ng/mL and 0.18 ng/mL for BUP, and 0.05 ng/mL and 0.20 ng/mL for norBUP, respectively, using a sample volume of 0.5 mL milk. BUP and norBUP concentrations determined from 10 random breast milk samples collected during 4 successive days from a lactating women during buprenorphine maintenance ranged from 1.0–14.7 and 0.6–6.3 ng/mL, respectively. Drug exposure of the infant may be considered to be low. Further investigations studies may seek to extend these preliminary findings to evaluate an infants' level of BUP exposure through breast milk.

Keywords: LC-MS/MS – buprenorphine – norbuprenorphine – breastfeeding