Detection by high-performance liquid chromatography of methotrexate and its metabolites in tumor tissue from osteosarcoma patients treated with high-dose methotrexate/leucovorin rescue.
Detection by high-performance liquid chromatography of methotrexate and its metabolites in tumor tissue from osteosarcoma patients treated with high-dose methotrexate/leucovorin rescue.
复制标题
采用高效液相色谱法检测接受大剂量甲氨蝶呤/亚叶酸救援治疗的骨肉瘤患者肿瘤组织中的甲氨蝶呤及其代谢物。
DOI：
10.1016/0006-2952(84)90685-3
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发表时间：
1984
影响因子：
5.8
通讯作者：
Rosen,G
中科院分区：
文献类型：
--
作者：
Samuels,LL;Feinberg,A;Moccio,DM;Sirotnak,FM;Rosen,G
在接受高剂量MTX/甲酰四氢叶酸补救治疗后24或48 h，从患者获得的成骨肉瘤肿瘤样本中检测到甲氨蝶呤（MTX）聚谷氨酸盐。通过高效液相色谱法测定肿瘤样品，并使用313 nm处的直接u. v.吸收和酶滴定法定量多聚谷氨酰代谢物（沿着MTX）。发现这两种方法之间的良好一致性，尽管更灵敏的酶测定法在一些样品中检测到紫外吸光度未检测到的峰。在研究的6个临床样本中发现MTX：MTX聚谷氨酸水平（1：1至25：1）的广泛变化。此外，未观察到聚谷氨酸盐形成程度与血浆水平（在肿瘤取样时测定）之间的相关性。高细胞内水平的衍生物，这似乎是MTX的7-羟基代谢物中也检测到四个6个样品。该物质与真实标准品共洗脱，显示出与标准品7-OH-MTX相似的光谱特性，并且不抑制二氢叶酸还原酶。
Methotrexate (MTX) polyglutamates were detected in osteogenic sarcoma tumor samples obtained from patients 24 or 48 h after receiving high-dose MTX/leucovorin rescue therapy. Tumor samples were assayed by high-performance liquid chromatography, and polyglutamyl metabolites, along with MTX, were quantitated using both direct u.v. absorption at 313 nm and an enzyme titration assay. Good agreement between these two methods was found although the more sensitive enzyme assay detected peaks in some samples not detected by u.v. absorbance. A wide variation in MTX:MTX polyglutamate levels (1:1 to 25:1) was found among the six clinical samples studied. Also, no correlation between the extent of polyglutamate formation and plasma levels (determined at the time of tumor sampling) was observed. High intracellular levels of a derivative which appears to be the 7-hydroxy metabolite of MTX were also detected in four of six samples. This material coeluted with authentic standard, showed spectral properties like standard 7-OH-MTX, and did not inhibit dihydrofolate reductase.