口服氟嘧啶类抗癌药S-1治疗患者泪液中5-氟尿嘧啶和替加氟的测定

Determination of 5-fluorouracil and tegafur in tear fluid of patients treated with oral fluoropyrimidine anticancer agent, S-1.

作者信息

Akune Yoko, Yamada Masakazu, Shigeyasu Chika

机构信息

Division for Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.

Department of Ophthalmology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan.

出版信息

Jpn J Ophthalmol. 2018 Jul;62(4):432-437. doi: 10.1007/s10384-018-0603-8. Epub 2018 Jun 21.

DOI:10.1007/s10384-018-0603-8

PMID:29931401

Abstract

PURPOSE

To establish a method for the measurement of 5-fluorouracil (5-FU), and tegafur (FT) in tear samples from patients treated with oral fluoropyrimidine anticancer agent S-1.

STUDY DESIGN

Cross-sectional study.

METHODS

High performance liquid chromatographic (HPLC) method reported for plasma samples was modified for tear samples. Simulated-tear solutions containing lactoferrin, lysozyme and standard solution containing 5-FU or FT were prepared for preliminary measurements. Tear samples from seven patients treated with S-1 were included. The tears were collected following S-1 administration using Schirmer's strips.

RESULTS

5-FU and FT concentrations of pure standard solution without extraction process were detected as original concentration. However, on extraction, FT samples in simulated-tear solution showed a peak for 5-FU but not for FT. FT was converted to 5-FU in the extraction process. Decomposition from FT to 5-FU was suppressed when 50 mg/mL bovine serum albumin was added during extraction. The mean concentrations of 5-FU and FT in tears during S-1 treatment were 0.17 ± 0.11 and 1.94 ± 0.71 μg/mL, respectively.

CONCLUSION

A simple HPLC method to determine 5-FU and FT in tear samples was established.

摘要

目的

建立一种测定口服氟嘧啶类抗癌药物S-1治疗患者泪液样本中5-氟尿嘧啶（5-FU）和替加氟（FT）的方法。

研究设计

横断面研究。

方法

对已报道的用于血浆样本的高效液相色谱（HPLC）方法进行修改以用于泪液样本。制备含有乳铁蛋白、溶菌酶的模拟泪液溶液以及含有5-FU或FT的标准溶液用于初步测量。纳入7例接受S-1治疗患者的泪液样本。使用泪液试纸在给予S-1后收集泪液。

结果

未经过提取过程的纯标准溶液中的5-FU和FT浓度检测为原始浓度。然而，在提取过程中，模拟泪液溶液中的FT样本显示出5-FU的峰，但未显示FT的峰。FT在提取过程中转化为5-FU。在提取过程中加入50 mg/mL牛血清白蛋白时，FT向5-FU的分解受到抑制。S-1治疗期间泪液中5-FU和FT的平均浓度分别为0.17±0.11和1.94±0.71μg/mL。