Quantification of naltrexone and 6,beta-naltrexol in plasma and milk using gas chromatography-mass spectrometry. Application to studies in the lactating sheep.
A selective gas chromatography-mass spectrometry method using solid-phase extraction has been developed for the detection and quantification of naltrexone and its metabolite, 6,beta-naltrexol in plasma and milk from humans and sheep at pharmacologically relevant concentrations. Di- or tri-acetyl derivatives were formed and quantified by selected-ion monitoring. Recoveries of naltrexone (30 microg/l) and 6,beta-naltrexol (250 microg/l) from both human plasma and milk were greater than 70%. Intra-assay and inter-day precision ranged from 3 to 21% for naltrexone and 2-18% for 6,beta-naltrexol for all matrices investigated, with an overall mean accuracy of 104% for naltrexone, and 99% for 6,beta-naltrexol. Human samples containing these analytes were stable for at least 3 weeks at -20 degrees C or 6 weeks at -80 degrees C. Analysis of the plasma and milk from the lactating sheep showed mean milk-to-plasma ratios of 55 for naltrexone and 3 for 6,beta-naltrexol.
Chan
C F
CF
Department of Pharmacology, The University of Western Australia, Crawley, Australia.
Chiswell
G M
GM
Bencini
R
R
Hackett
L P
LP
Dusci
L J
LJ
Ilett
K F
KF
D000818:Animals; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D007774:Lactation; D008892:Milk / Q000737:chemistry*; D009271:Naltrexone / Q000031:analogs & derivatives / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics; D009292:Narcotic Antagonists / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012756:Sheep
D009292:Narcotic Antagonists; C010410:6 beta-hydroxynaltrexone; D009271:Naltrexone