人生物基质中纳洛西醇的测定。

Determination of naloxegol in human biological matrices.

作者信息

Li Yan, Hoffmann Mark, Severin Paul

机构信息

Clinical Sample Science, Early Clinical Development, AstraZeneca, 35 Gatehouse Drive, Waltham, MA 02451, USA.

Covance Laboratories, Inc., 3301 Kinsman Blvd, Madison, WI 53704, USA.

出版信息

Bioanalysis. 2017 Apr;9(8):609-619. doi: 10.4155/bio-2016-0253. Epub 2017 May 15.

DOI:10.4155/bio-2016-0253

PMID:28504549

Abstract

AIM

Naloxegol is an oral peripherally acting μ-opioid receptor antagonist approved for the treatment of opioid-induced constipation. Sensitive, robust, bioanalytical methods were required to quantitate naloxegol in human biological matrices as part of the clinical development program.

METHODOLOGY/RESULTS: Analytical plasma samples were prepared using Solid Phase Extraction (SPE) coupled with concentration. The method's linearity was established at 0.1-50 ng/ml with up to 100-fold dilution. Urine samples were analyzed directly postdilution; dialysate samples were extracted by supported liquid extraction. Sensitive liquid chromatography/mass spectrometry (LC-MS/MS) assays were developed and validated, and demonstrated acceptable precision, accuracy and selectivity for naloxegol in the appropriate matrices.

CONCLUSION

Methods for quantifying naloxegol in human biological matrices have been successfully validated.

摘要

目的

纳洛西戈是一种口服外周作用的μ-阿片受体拮抗剂，已被批准用于治疗阿片类药物引起的便秘。作为临床开发项目的一部分，需要灵敏、可靠的生物分析方法来定量测定人体生物基质中的纳洛西戈。

方法/结果：采用固相萃取（SPE）结合浓缩法制备分析血浆样本。该方法在0.1 - 50 ng/ml范围内建立线性关系，稀释倍数可达100倍。尿液样本稀释后直接分析；透析液样本采用支持液液萃取法提取。开发并验证了灵敏的液相色谱/质谱（LC-MS/MS）分析方法，该方法在适当基质中对纳洛西戈具有可接受的精密度、准确度和选择性。