Xu Yang, Prohn Marita, Cai Xiaoyan, Crutchlow Michael, Shankar Sudha S, Bateman Kevin, Woolf Eric J
Regulated Bioanalysis, PPDM, 770 Sumneytown Pike, WP75B-300, West Point, PA 19486, USA.
Bioanalysis. 2014;6(24):3311-23. doi: 10.4155/bio.14.219.
A direct comparison of radioimmunoassay (RIA) and LC-MS/MS for insulin glargine quantification in human plasma is provided.
Compared with the RIA, the LC-MS/MS assay exhibited comparable/improved sensitivity (LLOQ at 0.1 ng/ml [˜16.7 pM or 2.8 μU/ml] for glargine and its metabolites M1 and M2, respectively) and ruggedness. Most importantly, it demonstrated a superior specificity advantage against the interference from endogenous insulin, exogenous insulin analogs (e.g., Novolog(®), Humalog(®) or Levemir(®), routine treatment for diabetes mellitus) and potentially pre-existing anti-insulin antibodies in patient samples. The data obtained from diabetic patients suggested the LC-MS/MS assay substantially improved pharmacokinetic characterization of glargine.
LC-MS/MS overcame common limitations of RIA, and provided critically needed specificity to support glargine clinical development, without sacrificing assay sensitivity and ruggedness.
本文对放射免疫分析法（RIA）和液相色谱-串联质谱法（LC-MS/MS）在人血浆中甘精胰岛素定量分析方面进行了直接比较。
与RIA相比，LC-MS/MS测定法具有相当的/更高的灵敏度（甘精胰岛素及其代谢物M1和M2的最低定量限分别为0.1 ng/ml [约16.7 pM或2.8 μU/ml]）和耐用性。最重要的是，它在内源性胰岛素、外源性胰岛素类似物（如诺和锐（®）、优泌乐（®）或来得时（®），糖尿病常规治疗药物）以及患者样本中可能预先存在的抗胰岛素抗体的干扰方面表现出卓越的特异性优势。从糖尿病患者获得的数据表明，LC-MS/MS测定法显著改善了甘精胰岛素的药代动力学特征。
LC-MS/MS克服了RIA的常见局限性，并在不牺牲测定灵敏度和耐用性的情况下，提供了支持甘精胰岛素临床开发急需的特异性。
