纳洛酮测定和nornaloxone (noroxymorphone)高性能液体chromatography-electrospray电离串联质谱分析。

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方白平衡,Chang Y, McCance-Katz EF,喜怒无常

纳洛酮测定和nornaloxone (noroxymorphone)高性能液体chromatography-electrospray电离串联质谱分析。

J肛门Toxicol。2009年10月,33(8):409 - 17所示。doi: 10.1093 / jat / 33.8.409。

PubMed ID

19874646 (在PubMed

]

文摘

高度敏感的方法被开发来衡量纳洛酮及其代谢物nornaloxone人血浆、尿液和人类肝脏微粒体(高)。Naltrexone-d(3)和oxymorphone-d(3)被用作各自的内部标准。固相萃取,使用混合模式提取0.1列和磷酸盐缓冲剂(pH值5.9),结合高效液相色谱法界面的电喷雾电离串联质谱分析。等离子体的校准范围是0.025到2对纳洛酮和0.5 ng / mL 20 nornaloxone ng / mL。10到2000 ng / mL在尿液和0.5的高20 ng / mL。酶法水解的尿液进行优化在40度为4 h c .内部和interrun精度在15%的目标;所有矩阵的精度在13.4%以内。纳洛酮的回收率分别为69.2%和32.0% nornaloxone。在血浆和尿液分析物稳定24 h后,等离子体在室温和三个冻融循环。在人类受试者接受16毫克丁丙诺啡和4毫克纳洛酮,烯丙羟吗啡酮检测了2 h在所有三个主题和4 h在一个主题。 Mean AUC(0-24) was 0.303 +/- 0.145 ng/mL.h; mean C(max) was 0.139 +/- 0.062 ng/mL; and T(max) was 0.5 h. In 24-h urine samples, about 55% of the daily dose was excreted in either conjugated or unconjugated forms of naloxone and nornaloxone in urine. When cDNA-expressed P450s were incubated with 20 ng of naloxone, nornaloxone formation was detected for P450s 2C18, 2C19, and 3A4. Naloxone utilization exceeded nornaloxone formation for 2C19 and 3A4, indicating they may produce products other than nornaloxone. These results demonstrate a new method suitable for both in vivo and in vitro metabolism and pharmacokinetic studies of naloxone.

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药物酶

药物	酶	类	生物	药理作用	行动
烯丙羟吗啡酮	细胞色素P450 2 c18	蛋白质	人类	未知的	底物	细节
烯丙羟吗啡酮	细胞色素P450 2 c19	蛋白质	人类	未知的	底物	细节
烯丙羟吗啡酮	细胞色素P450 3 a4	蛋白质	人类	未知的	底物 抑制剂	细节