LC-MS/MS method for quantification of 23 TKIs in Plasma: Assessing the relationship between anlotinib trough concentration and toxicities

LC-MS/MS method for quantification of 23 TKIs in Plasma: Assessing the relationship between anlotinib trough concentration and toxicities

•A simple, rapid and reliable LC-MS/MS method was developed and validated for quantifying 23 TKIs in plasma.•This study found a positive association between the trough concentration of anlotinib and the incidence of toxicities.•A model incorporating exposure level and platelet count demonstrated exc...

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Bibliographic Details
Published in:Clinica chimica acta Vol. 566; p. 120028
Main Authors: Bu, Chen, Jiang, Liansheng, Cui, Lili, Tang, Mao, Song, Xinhua, Zhao, Yingkui, Liang, Zhengyan, Ye, Liya, Nian, Jiayao, Gao, Shouhong, Tao, Xia, Wang, Zhipeng, Chen, Wansheng
Format: Journal Article
Language:English
Published: Elsevier B.V 01-01-2025
Subjects:
Anlotinib
Cancer
LC-MS/MS
Toxicities
Trough concentration
LLOQ
FDA
Trough concentration
DMSO
MRM
AUC
ADR
LC-MS/MS
SD
QC
M/Z
PLT
ESI
UHPLC
TDM
Anlotinib
RSD
OR
CI
MS
ROC
IS
CV
TKI
Toxicities
FA
Cancer
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Summary:•A simple, rapid and reliable LC-MS/MS method was developed and validated for quantifying 23 TKIs in plasma.•This study found a positive association between the trough concentration of anlotinib and the incidence of toxicities.•A model incorporating exposure level and platelet count demonstrated excellent diagnostic capacity for predicting ≥ 3 overall toxicities induced by anlotinib. To develop a simple, rapid, and sensitive LC-MS/MS method for quantifying 23 tyrosine kinase inhibitors (TKIs) in plasma samples, and evaluate the relationship between the trough concentration of anlotinib(ANL) and its toxicities. The method was developed in Agilent 1290–6460 UHPLC-MS/MS system. This study prospectively enrolled 55 cancer patients undergoing ANL treatment. Plasma samples were collected at steady-state trough concentration and subsequently analyzed using the method. Patients were recorded for the occurrence of toxicities. Statistical analysis was performed to assess the association of the toxicities with ANL exposure level and patients’ characteristics. The LC-MS/MS method was developed and validated for all items required by pharmacopoeia. The results revealed a positive association between the trough concentration of ANL and the incidence of toxicities. The exposure level 17.655 ng/mL (AUC 0.82, p = 0.010) was identified as a predictive threshold value for grade ≥ 3 overall toxicities. In addition, lower platelet count (PLT count < 179 × 109 g/L) was significantly associated with higher occurrence of grade ≥ 3 toxicities (AUC 0.75, p = 0.049). A logistic model incorporating these two factors demonstrated improved diagnostic capacity for predicting ≥ 3 overall toxicities (AUC = 0.90, p = 0.001). This study successfully developed and validated a simple, rapid, and sensitive LC-MS/MS method for quantifying 23 TKIs in plasma samples. Besides, this study found that both Ctrough of ANL and PLT count as independent predictors for ANL-induced ≥ 3 overall toxicities. Moreover, a logistic model including these two factors presents better prediction capacity for ≥ 3 overall toxicities.
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content type line 23
ISSN:0009-8981
1873-3492
1873-3492
DOI:10.1016/j.cca.2024.120028