Bioanalysis Zone

Non-capillary microsampling of plasma in rat and mice in support of GLP studies


Hans Stieltjes (Janssen Research & Development) has kindly provided Bioanalysis Zone a preview of his team’s novel research on non-capillary microsampling of plasma in rat and mice in support of GLP studies. Please note this work is pending peer-review.

Background: Different liquid microsampling techniques to obtain plasma samples have created great interest from toxicokinetic and pharmacokinetic scientists [1, 2]. These techniques enable reduction of sample volumes for exposure assessment in rodents and, consequently, serial profiles can be obtained from a single animal. In GLP safety studies, microsampling can remove the use of satellite animals. Although the full potential to reduce the sample volume is obtained with blood sampling and analysis, plasma remains the preferred matrix for exposure analysis. The current industry trend is to collect a small blood sample in capillaries. At Janssen, however, we initiated the collection of small volumes of blood (50—60 µL) into an appropriate adapted recipient to generate an accurate volume of 10 µL plasma in a more classical way.

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  1. Antonio Grondin on

    I am really surprised to hear about microsampling on mice with blood sampling volume of 60µl.
    I work in Drug Discovery for the oncology research center for small molecules at Pierre Fabre Laboratory. Nude mice are used daily. They are fragile animals and therefore great care must be used when manipulating them. Some strains are below 20g in weight and so 60µl of blood is a lot.
    Procédures have been developped 3 years ago to get early systemic exposure informations.
    The objective was to get those info while looking for DMT, a kind of “all in one” procedure. Since small animal were manipulated, serial microsampling was needed but also ease of procedure was compulsory in order to allow vivo staff to carry out both experiments. After experimenting several technologies, DBS technology turned out to be the best choice with accurate sampling volume of 10µl max. Everything has been optimised, from card type, sampling procedure, accurate drop sampling, whole spot extraction, extraction procedure…
    I work in Drug Discovery so a Drug Discovery tool is needed. But even for GLP studies where no-nude mice are being used, I don’t understand how 60µl-sampling volume in mice can be categorized as microsampling. I don’t see how serial microsampling can be carry out.

    • Hans Stieltjes on

      Dear Antonio, I fully agree that serial sampling in mice is not possible with 60 µL blood samples. The purpose is, however, not using serial sampling, but evaluation of toxicokinetics in the main tox animals. With the described approach the number of animals that is required for toxicokinetic evaluation can be reduced by about a factor of 4, compared to the original blood sampling approach of collecting close to 300 µL of blood.

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