用于血浆中 23 种 TKIs 定量的 LC-MS/MS 方法：评估安罗替尼谷浓度与毒性之间的关系

IF 3.2 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta Pub Date : 2024-11-14 DOI:10.1016/j.cca.2024.120028

Chen Bu , Liansheng Jiang , Lili Cui , Mao Tang , Xinhua Song , Yingkui Zhao , Zhengyan Liang , Liya Ye , Jiayao Nian , Shouhong Gao , Xia Tao , Zhipeng Wang , Wansheng Chen

{"title":"用于血浆中 23 种 TKIs 定量的 LC-MS/MS 方法：评估安罗替尼谷浓度与毒性之间的关系","authors":"Chen Bu , Liansheng Jiang , Lili Cui , Mao Tang , Xinhua Song , Yingkui Zhao , Zhengyan Liang , Liya Ye , Jiayao Nian , Shouhong Gao , Xia Tao , Zhipeng Wang , Wansheng Chen","doi":"10.1016/j.cca.2024.120028","DOIUrl":null,"url":null,"abstract":"<div><h3>Objectives</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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 × 10<sup>9</sup> 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).</div></div><div><h3>Conclusions</h3><div>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 C<sub>trough</sub> 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.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"566 ","pages":"Article 120028"},"PeriodicalIF":3.2000,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"LC-MS/MS method for quantification of 23 TKIs in Plasma: Assessing the relationship between anlotinib trough concentration and toxicities\",\"authors\":\"Chen Bu , Liansheng Jiang , Lili Cui , Mao Tang , Xinhua Song , Yingkui Zhao , Zhengyan Liang , Liya Ye , Jiayao Nian , Shouhong Gao , Xia Tao , Zhipeng Wang , Wansheng Chen\",\"doi\":\"10.1016/j.cca.2024.120028\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objectives</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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 × 10<sup>9</sup> 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).</div></div><div><h3>Conclusions</h3><div>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 C<sub>trough</sub> 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.</div></div>\",\"PeriodicalId\":10205,\"journal\":{\"name\":\"Clinica Chimica Acta\",\"volume\":\"566 \",\"pages\":\"Article 120028\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-11-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinica Chimica Acta\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0009898124022812\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICAL LABORATORY TECHNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinica Chimica Acta","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0009898124022812","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICAL LABORATORY TECHNOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

目的建立一种简便、快速、灵敏的LC-MS/MS方法，用于定量检测血浆样本中的23种酪氨酸激酶抑制剂（TKIs），并评估安罗替尼(ANL)的谷浓度与其毒性之间的关系：方法：采用安捷伦1290-6460 UHPLC-MS/MS系统开发了该方法。本研究前瞻性地纳入了55例接受安罗替尼治疗的癌症患者。采集稳态谷浓度的血浆样本，然后使用该方法进行分析。对患者的毒性反应进行记录。研究人员进行了统计分析，以评估毒性与ANL暴露水平和患者特征之间的关联：结果：开发并验证了LC-MS/MS方法的所有药典要求项目。结果表明，ANL的谷浓度与毒性反应的发生率呈正相关。暴露水平 17.655 ng/mL（AUC 0.82，p = 0.010）被确定为≥3 级总体毒性的预测阈值。此外，较低的血小板计数（PLT 计数 9 g/L）与较高的≥3 级毒性发生率显著相关（AUC 0.75，p = 0.049）。包含这两个因素的逻辑模型提高了预测≥3级总体毒性的诊断能力（AUC = 0.90，p = 0.001）：本研究成功开发并验证了一种简单、快速、灵敏的LC-MS/MS方法，用于定量检测血浆样本中的23种TKIs。此外，该研究还发现，ANL的Ctrough和PLT计数是ANL诱发≥3种总体毒性的独立预测因子。此外，包含这两个因素的逻辑模型对≥3种总体毒性有更好的预测能力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

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

Objectives

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.

Methods

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.

Results

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).

Conclusions

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 C_trough 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.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Clinica Chimica Acta 医学-医学实验技术

CiteScore

10.10

自引率

2.00%

发文量

1268

审稿时长

23 days

期刊介绍： The Official Journal of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Clinica Chimica Acta is a high-quality journal which publishes original Research Communications in the field of clinical chemistry and laboratory medicine, defined as the diagnostic application of chemistry, biochemistry, immunochemistry, biochemical aspects of hematology, toxicology, and molecular biology to the study of human disease in body fluids and cells. The objective of the journal is to publish novel information leading to a better understanding of biological mechanisms of human diseases, their prevention, diagnosis, and patient management. Reports of an applied clinical character are also welcome. Papers concerned with normal metabolic processes or with constituents of normal cells or body fluids, such as reports of experimental or clinical studies in animals, are only considered when they are clearly and directly relevant to human disease. Evaluation of commercial products have a low priority for publication, unless they are novel or represent a technological breakthrough. Studies dealing with effects of drugs and natural products and studies dealing with the redox status in various diseases are not within the journal''s scope. Development and evaluation of novel analytical methodologies where applicable to diagnostic clinical chemistry and laboratory medicine, including point-of-care testing, and topics on laboratory management and informatics will also be considered. Studies focused on emerging diagnostic technologies and (big) data analysis procedures including digitalization, mobile Health, and artificial Intelligence applied to Laboratory Medicine are also of interest.