Establishment and application of a method for the determination of plasma protein binding rate of imatinib and its metabolite / 中国药房
China Pharmacy
; (12): 2256-2260, 2022.
Article
Dans Zh
| WPRIM
| ID: wpr-943068
Responsable en Bibliothèque :
WPRO
ABSTRACT
OBJECTIVE To establish a method for the determination of plasma protein binding rate of imatinib and its metabolite(N-desmethyl imatinib )and apply it to patients with gastrointestinal stromal tumor (GIST).METHODS Using imatinib - d8 as the internal standard ,after being deproteinized methanol ,the sample was determined by equilibrium dialysis combined with liquid chromatography -tandem mass spectrometry . The free concentrations of imatinib and its metabolites in plasma of GIST patients were detected by the same method . RESULTS The protein binding rates of imatinib with albumin ,α1-acid glycoprotein and globulin at 120 ng/mL and 4 000 ng/mL were (92.5±1.0)% and(91.7±0.4)%,(56.6±2.0)% and(62.6±2.6)%,(56.3±3.1)% and (68.0±8.6)% ,respectively. The protein binding rates of N-desmethyl imatinib with albumin ,α1-acid glycoprotein and globulin at 60 ng/mL and 2 000 ng/mL were (90.6±3.5)% and(91.3±1.5)%,(54.1±5.1)% and(63.7±1.3)%,(56.2±7.6)% and(67.5±7.3)%,respectively. Compared with the low concentration group of imatinib (120 ng/mL)and its metabolite (60 ng/mL),the plasma protein binding rate of high concentration of imatinib (4 000 ng/mL)and its metabolite (2 000 ng/mL)with α1-acid glycoprotein and globulin was significantly increased (P< Δ基金项目 国家自然科学基金资助项目(No.81503160);江苏省 0.05),but there was no signifi -cant difference with albumin 卫生健康发展研究中心 2021年度开放课题(No.JSHD2021004);江苏 (P>0.05). In blank plasma ,the protein binding rates of imatinib(4 000 ng/mL)at high concentration and its metabolites(2 000 ng/mL)were significantly lower than those of low (120, 60 ng/mL) and medium (750, 375 ng/mL)concentration (P<0.01). Average protein binding rates of imatinib and its metabolite in plasma of GIST patients were (99.0±0.3)% and(99.2±0.3)%,respectively;the correlation coefficients between the concentrations of imatinib and its metabolites and the protein binding rates were -0.298 5 and -3.332 3,respectively(all P<0.05). CONCLUSIONS The method for determining the plasma protein binding rates of imatinib and its metabolites is successfully established . The plasma protein binding rates of imatinib and its metabolites in patients with GIST are negatively correlated with drug concentration .
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WPRIM
langue:
Zh
Texte intégral:
China Pharmacy
Année:
2022
Type:
Article