Comparison of pharmacokinetic study profiles of insulin in rat plasma through conventional sampling and microsampling by micro-LC–MS/MS: supplementary materials

Aim: With microsamples of blood, full pharmacokinetic profiles from individual animals can be obtained as
an alternative to the sparse-sampling approach, where conventional volume samples from several animals
are required. However, microsamples require assays that are more sensitive. Methods: The sensitivity of
the LC–MS assay was increased 47-fold using microflow LC–MS. Results & conclusion: By analyzing both
microsamples and conventional samples from the same animals, it is demonstrated that sparse-sampling
profiles can be nonrepresentative of the full profiles. This bias can affect the tested treatment by increasing
or reducing its apparent effect. Microsampling enables unbiased results compared with sparse-sampling.
An increase in assay sensitivity to balance the low sample volumes was achievable by microflow LC–MS.