Gutierrez P L, Cohen B E, Sosnovsky G, Davis T A, Egorin M J
Cancer Chemother Pharmacol. 1985;15(3):185-91. doi: 10.1007/BF00263883.
We defined the plasma and tissue concentrations and pharmacokinetics of SL-O-TT, a spin-labeled analog of thio-TEPA, in 35-44-g male Swiss Webster mice that had received spin-labeled thio-TEPA at a dosage of 10 mg/kg. Concentrations of spin-labeled thio-TEPA in ethyl acetate extracts of tissue and plasma were determined by gas-liquid chromatography and electron spin resonance spectroscopy. Plasma concentrations of spin-labeled thio-TEPA declined in a biexponential fashion that was well described by the equation: Ct = 21.5e-0.276t + 2.30e-0.026t indicating a half-life alpha of 2.5 min and a half-life beta of 26.6 min. After 2 h there was still spin-labeled thio-TE-PA in plasma, but not in tissues. In tissues, no spin-labeled thio-TEPA was detected with gas-liquid chromatography 15 min after injection, but with electron-spin resonance label was found in lung and skeletal muscle. The main metabolite of spin-labeled thio-TEPA is spin-labeled TEPA, where oxidative desulfurization is invoked as the main metabolic mechanism. Reduction of the spin label to the hydroxylamine was also observed with time.
我们测定了硫替派的自旋标记类似物SL-O-TT在体重35 - 44克的雄性瑞士韦伯斯特小鼠体内的血浆和组织浓度及药代动力学，这些小鼠接受了剂量为10毫克/千克的自旋标记硫替派。通过气液色谱法和电子自旋共振光谱法测定组织和血浆乙酸乙酯提取物中自旋标记硫替派的浓度。自旋标记硫替派的血浆浓度呈双指数下降，可用方程Ct = 21.5e-0.276t + 2.30e-0.026t很好地描述，表明α半衰期为2.5分钟，β半衰期为26.6分钟。2小时后，血浆中仍有自旋标记硫替派，但组织中没有。在组织中，注射后15分钟用气液色谱法未检测到自旋标记硫替派，但用电子自旋共振法在肺和骨骼肌中发现了标记物。自旋标记硫替派的主要代谢产物是自旋标记替派，主要代谢机制是氧化脱硫。随着时间的推移，还观察到自旋标记物还原为羟胺。
