Determination of Pyrrotinib Concentration in Human Plasma by LC-MS/MS and Its Clinical Application
- VernacularTitle:LC-MS/MS法测定人血浆中吡咯替尼的浓度及其临床应用
- Author:
Zhenhuan ZHAO
1
;
Weili JING
1
;
Tao LIU
1
;
Zhiqiang LYU
1
;
Zhihong CAO
1
;
Wen XU
1
Author Information
1. Dept. of Pharmacy，the Affiliated Hospital of Qingdao Universit y，Shandong Qingdao 266003，China
- Publication Type:Journal Article
- Keywords:
Pyrrotinib;
LC-MS/MS;
Imatinib;
Breast cancer;
Plasma concentration monitoring
- From:
China Pharmacy
2021;32(22):2767-2771
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE：To establish a method for the determination of pyrrotinib concentration in plasma ，and apply it in clinic. METHODS ：After precipitated with methanol ，the plasma sample was determined by LC-MS/MS using imatinib as internal standard. The determination was performed on Ultimate AQ-C 18 column with mobile phase consisted of methanol （containing 0.1％ formic acid ）and water （containing 0.1％ formic acid ）（gradient elution ）at the flow rate of 0.4 mL/min. The column temperature was 40 ℃，and the sample size was 5 µL. The ion source was electrospray ionization source ，and the positive ion scanning was carried out in multiple reaction mode. The ion pairs for quantitative analysis were m/z 583.4→138.3（pyrrotinib）and m/z 494.5→ 393.4（internal standard ），respectively. Thirty breast cancer patients taking pyrrotinib were collected from the Affiliated Hospital of Qingdao University during Jun.-Nov. 2020 to determine their steady-state trough concentrations of pyrrotinib after a week of treatment. RESULTS ：The linear range of pyrrotinib were 5-300 ng/mL（r＝0.999 3）. The lower limit of quantification was 5 ng/mL. RSDs of intra-day and inter-day were not higher than 9.30％，and relative errors （REs）ranged －6.70％-5.04％. REs of stability tests were in the range of －1.92％-5.42％. The extraction method ，matrix effect and residual effect did not affect the quantitative analysis of the substance to be tested. The steady-state trough concentrations of pyrrotinib were 32.6-82.8 ng/mL，with an average plasma concentration of 53.8 ng/mL；there was about 2.54 fold individual difference. CONCLUSIONS ：Established LC-MS/MS method is simple ，sensitive and accurate ，and can be used for the plasma concentration monitoring of pyrrotinib in breast cancer patient.
