Direct comparison of radioimmunoassay and LC–MS/MS for PK assessment of insulin glargine in clinical development. (December 2014)

• Record Type: Journal Article
• Authors: Xu, Yang; Prohn, Marita; Cai, Xiaoyan; Crutchlow, Michael; Shankar, Sudha S; Bateman, Kevin; Woolf, Eric J
• Is Part Of: Bioanalysis. Volume 6:Number 24(2014)
• Page Start: 3311
• Page End: 3323
• Publication Date: 2014-12
• Subjects: Drugs -- Analysis -- Periodicals; 615.19005
• DOI: 10.4155/bio.14.219
• Languages: English
• ISSNs: 1757-6180

Abstract

Background: A direct comparison of radioimmunoassay (RIA) and LC–MS/MS for insulin glargine quantification in human plasma is provided.Results: 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.Conclusion: LC–MS/MS overcame common limitations of RIA, and provided critically needed specificity to support glargine clinical development, without sacrificing assay sensitivity and ruggedness.