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Research Article

Direct comparison of radioimmunoassay and LC–MS/MS for PK assessment of insulin glargine in clinical development

    Yang Xu

    Regulated Bioanalysis, PPDM, 770 Sumneytown Pike, WP75B-300, West Point, PA 19486, USA

    ,
    Marita Prohn

    Quantitative Pharmacology & Pharmacometrics, PPDM, MSD BV, Molenstraat 110, 5342 CC, Oss, The Netherlands

    ,
    Xiaoyan Cai

    Biologics Bioanalytical Department,2015 Galloping Hill Road, Kenilworth, NJ 07033

    ,
    Michael Crutchlow

    Early Stage Clinical Biologics, 351 Sumneytown Pike, Mailstop 4D-48, North Wales PA 19454

    , ,
    Kevin Bateman

    Regulated Bioanalysis, PPDM, 770 Sumneytown Pike, WP75B-300, West Point, PA 19486, USA

    &
    Eric J Woolf

    Regulated Bioanalysis, PPDM, 770 Sumneytown Pike, WP75B-300, West Point, PA 19486, USA

    Published Online:https://doi.org/10.4155/bio.14.219

    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.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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