High-performance liquid chromatographic-electrospray mass spectrometric determination of morphine and its 3- and 6-glucuronides: application to pharmacokinetic studies.
A rapid and selective assay of morphine and its 3- and 6-glucuronides in serum, based on high-performance liquid chromatography-electrospray mass spectrometry has been developed. The analytes and the internal standard, codeine or naltrexone, were subjected to solid-phase extraction, using ethyl solid-phase extraction columns, prior to chromatography. A reversed-phase column and a gradient mobile phase consisting of water and methanol were used. The mass spectrometer was operated in the selected-ion monitoring mode. The following ions were used: m/z 286 for morphine, m/z 300 for codeine, m/z 342 for naltrexone, and m/z 462 for morphine 3- and 6-glucuronides. The limit of quantitation observed with this method was 10 ng/ml morphine, 50 ng/ml morphine-6-glucuronide and 100 ng/ml morphine-3-glucuronide. The present method proved useful for the determination of serum levels of the parent drug and its metabolites in pain patients, heroin addicts and in morphine-treated mice.
Pacifici
R
R
Clinical Biochemistry Department, Istituto Superiore di Sanità, Rome, Italy.
Pichini
S
S
Altieri
I
I
Caronna
A
A
Passa
A R
AR
Zuccaro
P
P
D000818:Animals; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D006556:Heroin Dependence / Q000097:blood; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000032:analysis* / Q000493:pharmacokinetics*; D009022:Morphine Derivatives / Q000032:analysis* / Q000493:pharmacokinetics*; D009369:Neoplasms / Q000097:blood; D012015:Reference Standards
D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D009020:Morphine; C018108:morphine-3-glucuronide