Che Jinjing, Wang Hui, Chen Zhihang, Li Xin, Hou Yunan, Shan Chengqi, Cheng Yuanguo
Department of Pharmacy, Beijing Institute of Microbiology and Epidemiology, 20 Dong-Da Street, Fengtai District, Beijing 100071, PR China.
J Pharm Biomed Anal. 2009 Sep 8;50(2):183-8. doi: 10.1016/j.jpba.2009.04.009. Epub 2009 Apr 16.
A novel assay method has been developed and validated, using surface plasmon resonance (SPR), for quantitation of cetuximab (C225) in monkey serum. By injecting non-labeled antibody samples onto a biosensor surface on which epidermal growth factor receptor (EGFR) was immobilized, the concentration of C225 can be accurately measured. This assay has a range of reliable response from 0.05 to 50 microg/ml C225 in monkey serum, which was well fitted with a sigmoidal model. The immobilized EGFR was found to be stable for at least 100 regeneration cycles at room temperature. Intra- and inter-assay CVs ranged from 3.20% to 8.89% and from 5.93% to 11.11%, accuracy from 92% to 107.52% and from 90% to 106.88%, respectively. Matrices such as 50% human serum, 50% Sprague Dawley rat serum, chimeric recombinant anti-CD20 monoclonal antibody, human gamma-globulin and chimeric recombinant her2 antibody did not interfere with C225 analysis on the sensor surface. This is the first report on the quantitation of C225 in monkey serum by an optical biosensor technology. This method was used to characterize the pharmacokinetics of C225 in rhesus monkeys. After a single-dose of intravenous infusion administration of 7.5, 24 and 75 microg/kg, average C(max) ranged from 168+/-28 to 1624+/-113 microg/ml, and AUC(0-infinity) ranged from 15,739+/-1059 to 295,017+/-44,533 microg h/ml. C225 elimination followed a bi-exponential profile with t(1/2) ranging from 2.7+/-0.7 to 6.7+/-0.1 h. It was non-linear serum pharmacokinetics of C225 across the investigated dosage range in monkeys (7.5-75 mg/kg).
已开发并验证了一种使用表面等离子体共振（SPR）定量猴血清中西妥昔单抗（C225）的新检测方法。通过将未标记的抗体样品注入固定有表皮生长因子受体（EGFR）的生物传感器表面，可准确测量C225的浓度。该检测在猴血清中对C225的可靠响应范围为0.05至50微克/毫升，与S形模型拟合良好。发现固定化的EGFR在室温下至少可稳定进行100次再生循环。批内和批间变异系数分别为3.20%至8.89%和5.93%至11.11%，准确度分别为92%至107.52%和90%至106.88%。诸如50%人血清、50%斯普拉格-道利大鼠血清、嵌合重组抗CD20单克隆抗体、人γ球蛋白和嵌合重组her2抗体等基质不会干扰传感器表面的C225分析。这是关于用光学生物传感器技术定量猴血清中C225的首篇报道。该方法用于表征恒河猴中C225的药代动力学。在单次静脉输注给药7.5、24和75微克/千克后，平均C(max)范围为168±28至1624±113微克/毫升，AUC(0-无穷大)范围为15,739±1059至295,017±44,533微克·小时/毫升。C225消除呈双指数分布，t(1/2)范围为2.7±0.7至6.7±0.1小时。在研究的猴剂量范围（7.5 - 75毫克/千克）内，C225的血清药代动力学呈非线性。
