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5-FU在全血中的稳定性及其TDM临床采样转运流程研究
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温永青 ，王文娟，白 羽，刘汝峰，马 旭（北京大学肿瘤医院暨北京市肿瘤防治研究所药剂科/恶性肿瘤发病
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机制及转化研究教育部重点实验室，北京 100142）
中图分类号 R917 文献标志码 A 文章编号 1001-0408（2025）23-2963-06
DOI 10.6039/j.issn.1001-0408.2025.23.14
摘 要 目的 考察5-氟尿嘧啶（5-FU）在人全血中的稳定性，并以此为依据建立标准化的5-FU治疗药物监测（TDM）临床采样转
运流程。方法 以EDTA抗凝全血样本为基质制备低（200 ng/mL）、高（5 000 ng/mL）浓度的5-FU全血稳定性考察样品（分别设置
无稳定剂组与添加1%体积比的稳定剂组）。将全血稳定性考察样品分别置于室温[（25±2）℃]及冷藏（2～8 ℃）条件下，于0、0.5、
1、2、4、7、24 h时间点取样处理，样品经涡旋、离心后取上层血浆，采用甲醇沉淀蛋白后，通过高效液相色谱-串联质谱法测定血浆
中5-FU的浓度。基于全血稳定性考察结果制定临床采样转运流程。结果 未添加稳定剂的空白全血样品中5-FU的浓度显著低
于添加了稳定剂的样品（P＜0.05），而不同体积（10、25、50 μL）稳定剂对低、高浓度全血稳定性考察样品中5-FU的浓度测定结果
均无显著影响（P＞0.05）。未添加稳定剂时，低、高浓度的5-FU全血样品在室温下分别可稳定保存0.5 h与1 h，冷藏条件下分别可
稳定保存2 h与7 h；添加1%体积比的稳定剂后，全血样品在室温与冷藏条件下均可稳定保存24 h。所建5-FU TDM临床采样转
运流程为：采样后将全血样本在室温（≤0.5 h）或4 ℃（≤2 h）条件下暂存，并于2～8 ℃冷藏转运；送达实验室后立即添加1%体积
比的稳定剂，并于24 h内完成离心，所得血浆于－20 ℃保存。结论 全血中的5-FU在室温条件下稳定性较差，2～8 ℃冷藏时稳定
性略有提升但仍会快速降解；添加1%体积比的稳定剂可显著延长其冷藏保存时间。本研究所建5-FU TDM临床采样转运流程，
创新性地将稳定剂添加节点设置于样品接收环节（而非采血后立即添加），在保证样品分析质量的前提下，更贴合临床采血的实际
操作条件，显著提升了临床实际操作的可行性。
关键词 5-氟尿嘧啶；全血；稳定性；治疗药物监测；临床采样转运流程
Stability of 5-FU in whole blood and a clinical sampling and delivery procedures for TDM
WEN Yongqing，WANG Wenjuan，BAI Yu，LIU Rufeng，MA Xu[Dept. of Pharmacy， Peking University Cancer
Hospital & Institute/Key Laboratory of Carcinogenesis and Translational Research （Ministry of Education），
Beijing 100142， China]
ABSTRACT OBJECTIVE To investigate the stability of 5-fluorouracil （5-FU） in human blood and to establish a standardized
clinical sampling and delivery procedure for therapeutic drug monitoring （TDM） of 5-FU. METHODS The EDTA-anticoagulated
whole blood was used as the matrix to prepare stability assessment samples of 5-FU at both low （200 ng/mL） and high （5 000
ng/mL） concentrations （with groups without stabilizer and with 1% volume ratio of stabilizer）. The stability assessment samples
were placed under room temperature [（25±2） ℃] and refrigerated （2-8 ℃） conditions， with sampling at 0， 0.5， 1， 2， 4， 7， and
24 h. After vortexing and centrifugation， the upper plasma layer was collected； proteins were precipitated using methanol， and the
concentration of 5-FU in plasma was determined by liquid chromatography-tandem mass spectrometry. Based on the whole blood
stability results， clinical sampling and delivery procedures were established. RESULTS The concentration of 5-FU in blank whole
blood samples without stabilizers was significantly lower than that in samples with stabilizers （P＜0.05）. However， varying
volumes （10， 25， 50 μL） of stabilizers had no significant effect on the measured concentrations of 5-FU in stability assessment
samples with low and high concentrations （P＞0.05）. Without the addition of a stabilizer， low- and high-concentration 5-FU whole
blood samples remained stable at room temperature for 0.5 h and 1 h， respectively， and under refrigeration for 2 h and 7 h，
respectively. After the addition of a 1% stabilizer， the whole blood samples remained stable for up to 24 h under both room
temperature and refrigerated conditions. Based on these findings， the following procedure was established： after collection， whole
blood samples could be temporarily stored at room temperature （≤0.5 h） or at 4 ℃ （≤2 h）， and transported at 2-8 ℃. Upon
delivery to the laboratory， a 1% volume ratio of stabilizer must be added immediately， followed by centrifugation within 24 h. The
resulting plasma should be stored at －20 ℃. CONCLUSIONS 5-FU in whole blood exhibits poor stability at room temperature.
Refrigeration at 2-8 ℃ slightly improves stability， but
degradation still occurs rapidly. Adding a stabilizer at a 1%
Δ 基金项目 北京大学肿瘤医院科学研究基金项目（No.JC202409）
＊第一作者 药师，硕士。研究方向：治疗药物监测、药物分析。 volume ratio significantly prolongs the refrigerated storage
E-mail：wenyongqing@vip.163.com time. The established sampling and transport procedure for 5-
# 通信作者 副主任药师，博士。研究方向：临床药学、肿瘤精准药 FU TDM innovatively introduces the stabilizer addition step at
学。E-mail：maxu1985@bjmu.edu.cn the laboratory sample reception stage （rather than immediately
中国药房 2025年第36卷第23期 China Pharmacy 2025 Vol. 36 No. 23 · 2963 ·
