一种通过液相色谱-串联质谱法同时测量总抗体和可裂解抗体偶联药物的通用方法。
A generic approach for simultaneous measurements of total antibody and cleavable antibody-conjugated drug by LC/MS/MS.
作者信息
Xu Ling, Packer Laura E, Li Chao, Abdul-Hadi Kojo, Veiby Petter
机构信息
Mersana Therapeutics Inc., 840 Memorial Drive, Cambridge, MA 02139, USA; Millennium Pharmaceuticals, Inc., A Wholly Owned Subsidiary of Takeda Pharmaceutical Company Limited, 35 Landsdowne Street, Cambridge, MA 02139, USA.
Millennium Pharmaceuticals, Inc., A Wholly Owned Subsidiary of Takeda Pharmaceutical Company Limited, 35 Landsdowne Street, Cambridge, MA 02139, USA.
出版信息
Anal Biochem. 2017 Nov 15;537:33-36. doi: 10.1016/j.ab.2017.08.024. Epub 2017 Sep 1.
The current industry practice for antibody-drug conjugate (ADC) bioanalysis includes quantification of total antibody and antibody-conjugated drug. Here, we report a novel 2-in-1 approach for measuring total antibody and protease-cleavable conjugated drug Monomethyl Auristatin E (MMAE) concurrently. This allows for the determination of the DAR (Drug Antibody Ratio) for in vivo samples, with a 3-orders linear range based on total antibody concentration from 0.1 to 100 μg/mL. Our generic, concurrent method has been cross-validated with the previously established methods in an animal study. This novel approach is applicable to all human IgG1 ADCs with papain cleavable conjugated drug in preclinical studies.
目前抗体药物偶联物（ADC）生物分析的行业惯例包括对总抗体和抗体偶联药物进行定量。在此，我们报告了一种新颖的二合一方法，可同时测量总抗体和蛋白酶可裂解的偶联药物单甲基奥瑞他汀E（MMAE）。这使得能够测定体内样品的药物抗体比（DAR），基于总抗体浓度在0.1至100μg/mL范围内具有3个数量级的线性范围。我们通用的同时检测方法已在一项动物研究中与先前建立的方法进行了交叉验证。这种新颖的方法适用于临床前研究中所有具有可被木瓜蛋白酶裂解的偶联药物的人IgG1 ADC。
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