Hofmann U, Seefried S, Schweizer E, Ebner T, Mikus G, Eichelbaum M
Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, Stuttgart, Germany.
J Chromatogr B Biomed Sci Appl. 1999 Apr 30;727(1-2):81-8. doi: 10.1016/s0378-4347(99)00090-0.
A sensitive and specific method was developed for the determination of codeine and morphine in human serum and for the determination of trace amounts of endogenous morphine in human urine. The analytes were recovered from serum by a simple liquid-liquid extraction method. Urine samples were hydrolyzed, and purified by two liquid-liquid extraction steps and a solid-phase extraction. Samples were derivatized to the pentafluoropropionic esters and measured by gas chromatography tandem mass spectrometry. Using the deuterated analogues as internal standards a limit of quantification of 20 fmol/ml (5.7 pg/ml) morphine and 500 fmol/ml (150 pg/ml) codeine in human serum and of 2.5 fmol/ml (0.71 pg/ml) morphine in urine was achieved. The method was suitable for the determination of morphine and codeine in pharmacokinetic studies and for the determination of the urinary excretion of endogenous morphine.
开发了一种灵敏且特异的方法，用于测定人血清中的可待因和吗啡，以及测定人尿中痕量内源性吗啡。通过简单的液-液萃取法从血清中回收分析物。尿样经水解处理，并通过两步液-液萃取和固相萃取进行纯化。样品衍生化为五氟丙酸酯，并用气相色谱串联质谱法进行测定。以氘代类似物作为内标，人血清中吗啡的定量限为20 fmol/ml（5.7 pg/ml）、可待因的定量限为500 fmol/ml（150 pg/ml），尿中吗啡的定量限为2.5 fmol/ml（0.71 pg/ml）。该方法适用于药代动力学研究中吗啡和可待因的测定，以及内源性吗啡尿排泄量的测定。
