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

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.