Simultaneous and Rapid Determination of Six Tyrosine Kinase Inhibitors in Patients with Non-Small Cell Lung Cancer Using HPLC-MS/MS

Objective. To develop a new method for quantitatively analyzing six tyrosine kinase inhibitors (gefitinib, erlotinib, icotinib, afatinib, osimertinib, and crizotinib) used in the treatment of non-small cell lung cancer (NSCLC) by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Methods. Th...

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Main Authors: Yanping Liu, Hua Liu, Zhewei Xia, Zhipeng Wang, Yunlei Yun, Guanying Zhang, Lifeng Huang, Shouhong Gao, Wansheng Chen
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:International Journal of Analytical Chemistry
Online Access:http://dx.doi.org/10.1155/2021/5524361
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author Yanping Liu
Hua Liu
Zhewei Xia
Zhipeng Wang
Yunlei Yun
Guanying Zhang
Lifeng Huang
Shouhong Gao
Wansheng Chen
author_facet Yanping Liu
Hua Liu
Zhewei Xia
Zhipeng Wang
Yunlei Yun
Guanying Zhang
Lifeng Huang
Shouhong Gao
Wansheng Chen
author_sort Yanping Liu
collection DOAJ
description Objective. To develop a new method for quantitatively analyzing six tyrosine kinase inhibitors (gefitinib, erlotinib, icotinib, afatinib, osimertinib, and crizotinib) used in the treatment of non-small cell lung cancer (NSCLC) by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Methods. The analytes were detected in the selected reaction monitoring mode on a triple quadrupole mass spectrometer with the positive ionization mode. Carbamazepine was utilized as the internal standard. The pretreatment of the plasma sample was completed based on protein precipitation with acetonitrile, and the analytes were separated on an Agilent Zorbax SB-C18 reversed-phase column (2.1 mm × 100 mm, 3.5 μm, Agilent, USA) using gradient elution. The mobile phase consisted of 0.1% formic acid in water (phase A) and 0.1% formic acid in acetonitrile (phase B). The flow rate was 0.3 mL/min, and the injection volume was 5 μL. The column temperature was set and maintained at 35°C. Results. The calibration curves were linear over the range from 5.0 to 1000.0 ng/mL for gefitinib, crizotinib, and osimertinib; from 50.0 to 4000.0 ng/mL for icotinib and erlotinib; and from 5.0 to 400.0 ng/mL for afatinib. Linear correlation coefficients were >0.990 for all regression curves. The intra- and interday accuracy and precision of the method were within ±15.0% and not more than 15.0%, respectively. The mean recovery of all the analytes ranged from 70.18% to 110.76%, the matrix effect was from 88.85% to 127.58%, and stability was within ±15.0%. Conclusion. This newly developed method was sensitive, simple, and robust and could be used in therapeutic drug monitoring of six tyrosine kinase inhibitors in NSCLC patients.
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spelling doaj-art-aedbf0f56ec24cd5a6e69fede3a1505e2025-08-20T02:23:08ZengWileyInternational Journal of Analytical Chemistry1687-87601687-87792021-01-01202110.1155/2021/55243615524361Simultaneous and Rapid Determination of Six Tyrosine Kinase Inhibitors in Patients with Non-Small Cell Lung Cancer Using HPLC-MS/MSYanping Liu0Hua Liu1Zhewei Xia2Zhipeng Wang3Yunlei Yun4Guanying Zhang5Lifeng Huang6Shouhong Gao7Wansheng Chen8Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, ChinaDepartment of Pharmacy, Taixing People’s Hospital, Taizhou, Jiangsu 225400, ChinaPharmaceutical Analysis and Testing Center, School of Pharmacy, The Second Military Medical University, Shanghai 200003, ChinaDepartment of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, ChinaDepartment of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, ChinaDepartment of Pharmacy, The Affliated Suzhou Science and Technology Town Hospital of Nanjing Medical University, Suzhou 215153, ChinaDepartment of Pharmacy, The Affliated Suzhou Science and Technology Town Hospital of Nanjing Medical University, Suzhou 215153, ChinaDepartment of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, ChinaDepartment of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, ChinaObjective. To develop a new method for quantitatively analyzing six tyrosine kinase inhibitors (gefitinib, erlotinib, icotinib, afatinib, osimertinib, and crizotinib) used in the treatment of non-small cell lung cancer (NSCLC) by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Methods. The analytes were detected in the selected reaction monitoring mode on a triple quadrupole mass spectrometer with the positive ionization mode. Carbamazepine was utilized as the internal standard. The pretreatment of the plasma sample was completed based on protein precipitation with acetonitrile, and the analytes were separated on an Agilent Zorbax SB-C18 reversed-phase column (2.1 mm × 100 mm, 3.5 μm, Agilent, USA) using gradient elution. The mobile phase consisted of 0.1% formic acid in water (phase A) and 0.1% formic acid in acetonitrile (phase B). The flow rate was 0.3 mL/min, and the injection volume was 5 μL. The column temperature was set and maintained at 35°C. Results. The calibration curves were linear over the range from 5.0 to 1000.0 ng/mL for gefitinib, crizotinib, and osimertinib; from 50.0 to 4000.0 ng/mL for icotinib and erlotinib; and from 5.0 to 400.0 ng/mL for afatinib. Linear correlation coefficients were >0.990 for all regression curves. The intra- and interday accuracy and precision of the method were within ±15.0% and not more than 15.0%, respectively. The mean recovery of all the analytes ranged from 70.18% to 110.76%, the matrix effect was from 88.85% to 127.58%, and stability was within ±15.0%. Conclusion. This newly developed method was sensitive, simple, and robust and could be used in therapeutic drug monitoring of six tyrosine kinase inhibitors in NSCLC patients.http://dx.doi.org/10.1155/2021/5524361
spellingShingle Yanping Liu
Hua Liu
Zhewei Xia
Zhipeng Wang
Yunlei Yun
Guanying Zhang
Lifeng Huang
Shouhong Gao
Wansheng Chen
Simultaneous and Rapid Determination of Six Tyrosine Kinase Inhibitors in Patients with Non-Small Cell Lung Cancer Using HPLC-MS/MS
International Journal of Analytical Chemistry
title Simultaneous and Rapid Determination of Six Tyrosine Kinase Inhibitors in Patients with Non-Small Cell Lung Cancer Using HPLC-MS/MS
title_full Simultaneous and Rapid Determination of Six Tyrosine Kinase Inhibitors in Patients with Non-Small Cell Lung Cancer Using HPLC-MS/MS
title_fullStr Simultaneous and Rapid Determination of Six Tyrosine Kinase Inhibitors in Patients with Non-Small Cell Lung Cancer Using HPLC-MS/MS
title_full_unstemmed Simultaneous and Rapid Determination of Six Tyrosine Kinase Inhibitors in Patients with Non-Small Cell Lung Cancer Using HPLC-MS/MS
title_short Simultaneous and Rapid Determination of Six Tyrosine Kinase Inhibitors in Patients with Non-Small Cell Lung Cancer Using HPLC-MS/MS
title_sort simultaneous and rapid determination of six tyrosine kinase inhibitors in patients with non small cell lung cancer using hplc ms ms
url http://dx.doi.org/10.1155/2021/5524361
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