Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, China.
Rapid Commun Mass Spectrom. 2022 Nov 15;36(21):e9372. doi: 10.1002/rcm.9372.
Anlotinib is a multi-target tyrosine kinase inhibitor, approved in China for treating several cancer types. Dose individualization based on therapeutic drug monitoring (TDM) is a useful tool to reduce toxicity. However, it is not convenient for patients to go to hospital for routine TDM via venous blood sampling at a certain time.
An ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for determination of anlotinib in human plasma and dried blood spot (DBS), characterized by simple sample preparation, high sensitivity, and short analysis time. The assay was validated in the concentration range of 0.2-200 ng/mL in plasma and 5-1000 ng/mL in DBS. This method was applied to monitor anlotinib exposure levels in patients with advanced biliary tract cancer (BTC) and non-small cell lung cancer (NSCLC).
The trough plasma concentration (C ) of anlotinib was highly variable among BTC patients with coefficients of variation (CV) of 47.5%. DBS and venous blood samples were also collected from NSCLC patients to determine whether DBS sampling is a viable alternative sampling approach. Pearson correlation coefficient (R) between DBS and plasma concentration was 0.985. Bland-Altman plot demonstrated that the difference between estimated and measured plasma concentration was -2.9%. And 87% of sample pairs had a maximal deviation of ±20%.
Anlotinib exhibits a high inter-individual variability in plasma exposure, and DBS sampling could be a promising tool for TDM of anlotinib.
安罗替尼是一种多靶点酪氨酸激酶抑制剂，在中国被批准用于治疗多种癌症。基于治疗药物监测（TDM）的剂量个体化是减少毒性的有用工具。然而，患者通过静脉血样在特定时间到医院进行常规 TDM 并不方便。
建立并验证了一种超高效液相色谱串联质谱（UPLC-MS/MS）法，用于测定人血浆和干血斑（DBS）中的安罗替尼，该方法具有样品制备简单、灵敏度高、分析时间短的特点。该测定法在血浆中的浓度范围为 0.2-200ng/mL 和 DBS 中的浓度范围为 5-1000ng/mL 进行了验证。该方法用于监测晚期胆道癌（BTC）和非小细胞肺癌（NSCLC）患者的安罗替尼暴露水平。
BTC 患者的安罗替尼谷浓度（C）个体间差异很大，变异系数（CV）为 47.5%。还从 NSCLC 患者中采集了 DBS 和静脉血样，以确定 DBS 采样是否是一种可行的替代采样方法。DBS 与血浆浓度之间的 Pearson 相关系数（R）为 0.985。Bland-Altman 图表明估计的和测量的血浆浓度之间的差异为-2.9%。并且 87%的样本对的最大偏差为±20%。
安罗替尼在血浆暴露中表现出高度的个体间变异性，DBS 采样可能是 TDM 安罗替尼的一种有前途的工具。
