Establishment and clinical application of the method for the determination of blood concentration of apatinib

DUAN Xianchun; XUE Sujun; ZHU Yongfu

doi:10.6039/j.issn.1001-0408.2024.12.15

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Establishment and clinical application of the method for the determination of blood concentration of apatinib

更新时间：2025-09-26

- Establishment and clinical application of the method for the determination of blood concentration of apatinib
- ZHONGGUO YAOFANG Vol. 35, Issue 12, Pages: 1500-1504(2024)
- 作者机构：
  
  1.安徽中医药大学第一附属医院药学部，合肥　230031
  2.安徽中医药大学新安医学教育部重点实验室，合肥　230012
  3.安徽中医药大学第一附属医院肿瘤一科，合肥　230031
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2024.12.15
  CLC： R979.1;R969.1
- Received：27 February 2024，
  
  Revised：2024-03-20，
  
  Accepted：07 May 2024，
  
  Published：30 June 2024
- 稿件说明：
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段贤春,薛苏君,祝永福.阿帕替尼血药浓度测定方法的建立及临床应用[J].中国药房,2024,35(12):1500-1504.

DUAN Xianchun,XUE Sujun,ZHU Yongfu.Establishment and clinical application of the method for the determination of blood concentration of apatinib[J].ZHONGGUO YAOFANG,2024,35(12):1500-1504.
段贤春,薛苏君,祝永福.阿帕替尼血药浓度测定方法的建立及临床应用[J].中国药房,2024,35(12):1500-1504. DOI： 10.6039/j.issn.1001-0408.2024.12.15.

DUAN Xianchun,XUE Sujun,ZHU Yongfu.Establishment and clinical application of the method for the determination of blood concentration of apatinib[J].ZHONGGUO YAOFANG,2024,35(12):1500-1504. DOI： 10.6039/j.issn.1001-0408.2024.12.15.

摘要

目的

建立测定阿帕替尼血药浓度的方法并进行临床应用。

方法

采用超高效液相色谱（UPLC）法进行血药浓度测定，色谱柱为ACQUITY UPLC BEH C

，流动相为乙腈-0.1%甲酸水溶液（梯度洗脱），流速为0.2 mL/min，柱温为40 ℃，进样量为5 μL。收集26例服用阿帕替尼癌症患者的病例资料，检测其血药浓度，分析阿帕替尼血药浓度与患者年龄、给药剂量、不良反应及联合用药的相关性，并检测患者治疗前后血清肾损伤相关因子[胱抑素C（CysC）、肾损伤分子1（KIM-1）、白细胞介素18（IL-18）、肿瘤坏死因子α（TNF-α）

]

水平。

结果

阿帕替尼检测质量浓度在500～2 000 ng/mL范围内线性关系良好，精密度试验RSD为3.7%，稳定性试验RSD为4.9%，平均加样回收率为96.0%（RSD为2.1%）。26例患者的阿帕替尼血药浓度最低为103 ng/mL，最高为1 932 ng/mL。患者的血药浓度随年龄呈波动降低趋势。在0.125或0.25 g给药剂量下，服用阿帕替尼的患者体内血药浓度集中在1 000～2 000 ng/mL范围内。26例癌症患者中有13例发生不良反应，其中血药浓度500～＜1 000 ng/mL者未见不良反应发生。20例患者同时联用了其他药物，其血药浓度高低不同。治疗后，患者的血清CysC、KIM-1、IL-18、TNF-α水平均显著高于治疗前（

＜0.05）。

结论

所建立的UPLC方法能快速检测阿帕替尼血药浓度。临床使用阿帕替尼时应综合考虑患者年龄和药物联用等情况，并注意防范阿帕替尼可能导致的急性肾损伤。

Abstract

OBJECTIVE

To establish a method for determining the blood concentration of apatinib and apply it clinically.

METHODS

Ultra-high performance liquid chromatography （UPLC） was used for the determination of blood concentration. The chromatographic column was ACQUITY UPLC BEH C

with the mobile phase consisted of acetonitrile-0.1% formic acid aqueous solution （gradient elution） at the flow rate of 0.2 mL/min； the column temperature was 40 ℃， and the injection volume was 5 μL. The data of 26 cancer patients taking apatinib were collected， and their blood concentrations were measured. The correlation between patient’s blood concentration and age， dosage， adverse reactions， and combination therapy were analyzed； the levels of serum kidney injury-related factors [cystatin C （CysC）， kidney injury molecule 1 （KIM-1）， interleukin-18 （IL-18）， tumor necrosis factor-α （TNF-α）

]

were determined before and after treatment.

RESULTS

The linear range of apatinib was 500-2 000 ng/mL， with a precision RSD of 3.7%， stability RSD of 4.9%， and an average sample recovery rate of 96.0% （RSD was 2.1%）. The lowest blood concentration of apatinib was 103 ng/mL and the highest was 1 932 ng/mL among 26 patients. The blood concentration of apatinib in patients showed a fluctuating downward trend with age. At a dosage of 0.125 or 0.25 g， the blood concentration of patients taking apatinib was concentrated within the range of 1 000-2 000 ng/mL. Among 26 cancer patients， 13 experienced adverse reactions， and no adverse reaction was observed in those with blood concentrations ranging from 500 to ＜1 000 ng/mL. Twenty patients were simultaneously treated with other drugs， resulting in varying blood concentration. After treatment， the levels of serum CysC， KIM-1， IL-18 and TNF-α were significantly higher than before treatment （

＜0.05）.

CONCLUSIONS

The established UPLC method can quickly detect the blood concentration of apatinib. When using apatinib in clinical practice， comprehensive consideration should be given to the patient’s age， drug combination， and the attention should be paid to preventing possible acute kidney damage caused by apatinib.

关键词

Keywords

references

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