UPLC-ESI-MS/MS study of the effect of green tea extract on the oral bioavailability of erlotinib and lapatinib in rats: Potential risk of pharmacokinetic interaction
UPLC-ESI-MS/MS study of the effect of green tea extract on the oral bioavailability of erlotinib and lapatinib in rats: Potential risk of pharmacokinetic interaction
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DOI：
10.1016/j.jchromb.2017.02.029
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发表时间：
2017-04-01
影响因子：
3
通讯作者：
Abahussain, Ashwag O.
中科院分区：
文献类型：
--
作者：
Maher, Hadir M.;Alzoman, Nourah Z.;Abahussain, Ashwag O.
绿色茶（GT）是全球消费量最大的饮料之一。酪氨酸激酶抑制剂（Tyrosine kinase inhibitors，TKI）是近年来备受关注的口服靶向治疗药物，其中埃罗替尼（Erlotinib，ERL）和拉帕替尼（Lapatinib，RP 10）是最受关注的两类药物。由于已知绿色茶多酚（GTP）是受体酪氨酸激酶的抑制剂，因此GTE可能增强TKI的抗癌作用，但可能与联合给药的TKI发生药代动力学（PK）相互作用。本实验研究了GTE对大鼠ERL/ERL模型PLC的影响。以吉非替尼（GEF）为内标物，建立了大鼠血浆中ERL和ERB的UPLC-ESI-MS/MS定量方法，并进行了验证。血浆样品通过蛋白沉淀（PPT）进行广泛处理，然后使用十八烷基C18/14%柱进行固相萃取（SPE）。在Acquity UPLC BEHTM C18柱上进行色谱分析，移动的相由水：乙腈（20：80，v/v）组成，各含0.15%甲酸。以正电喷雾电离（ESI +）模式进行定量，其中多反应监测（MRM）跃迁m/z 394.29 -> 4 278.19（ERL）、m/z 581.07 -> 365.13（EFL）和m/z 447.08 -> 128.21（GEF）。根据FDA指导原则对该方法进行了充分验证，结果显示在0.4-1000（ERL）和0.6-1000（μ g）ng/mL范围内呈线性，ERL和μ g的定量下限（LLOQ）极低，分别为0.4和0.6 ng/mL。将该方法的适用性扩展到对GTE短期和长期给药后ERL/ERP 3的PK进行比较研究，并与单次口服给药进行比较。结果显示，在摄入GTE后，ERL和GTE的口服生物利用度均显著降低，特别是短期给药。GTE短期给药记录到C-max（AUC）分别降低67.60%（69.50%）和70.20%（73.96%），而ERL和GTE长期给药仅分别降低16.03%（21.09%）和13.53%（22.12%）。因此，服用TKI的患者在TKI治疗期间最好避免饮用GT或摄入GTE胶囊。(C)2017爱思唯尔B. V.保留所有权利。
Green tea (GT) is one of the most consumed beverages worldwide. Tyrosine kinase inhibitors (TKIs) belong to the oral targeted therapy that gained much interest in oncology practice, among which are erlotinib (ERL) and lapatinib (LAP). Since green tea polyphenols (GTP) are known to be inhibitors of receptor tyrosine kinases, GTE could likely potentiate the anticancer effect of TKIs, but with a possibility of pharmacokinetic (PK) interaction with co -administered TKIs. In this study, the effect of GTE on the PLC of ERL/LAP in rats was studied. UPLC-ESI-MS/MS method has been developed and validated for the quantification of ERL and LAP in rat plasma, using gefitinib (GEF) as the internal standard. Plasma samples were treated extensively by protein precipitation (PPT) followed by solid phase extraction (SPE) using octadecyl C 18/14% cartridges. Chromatographic analysis was carried out on Acquity UPLC BEHTM C18 column with a mobile phase consisting of water: acetonitrile (20: 80, v/v), each with 0.15% formic acid. Quantification was performed in the positive electrospray ionization (ESI +) mode with multiple reaction monitoring (MRM) of the transitions m/z 394.29 -> 4 278.19 (ERL), m/z 581.07 -> 365.13 (LAP), and m/z 447.08 -> 128.21 (GEF). The method was fully validated as per the FDA guidelines showing linearity over the range of 0.4-1000 (ERL) and 0.6-1000 (LAP) ng/mL with very low lower limit of quantification (LLOQ) of 0.4 and 0.6 ng/mL for ERL and LAP, respectively. The applicability of the method was extended to perform a comparative study of the PK of ERL/LAP following short-term and long-term administration of GTE, compared with their single oral administration. The results revealed that a significant reduction in the oral bioavailability was recorded with both ERL and LAP following the ingestion of GTE particularly for short-term administration. A reduction in C-max (AUC) by 67.60% (69.50%) and 70.20% (73.96%), was recorded with short-term administration of GTE, compared with only 16.03% (21.09%) and 13.53% (22.12%) reduction for ERL and LAP, respectively, with long-term administration. Thus patients taking TKIs should preferably avoid drinking GT or ingesting GTE capsules during the period of treatment with TKIs.(C) 2017 Elsevier B.V. All rights reserved.