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.

目的：通过利用微量的血液样本，可获取个体动物的完整药代动力学特征，此方法作为一种替代传统稀疏采样技术的手段，后者需从多只动物中获取常规体积样本。然而，微样本的检测需要更为灵敏的检测方法。方法：采用微流液相色谱-质谱联用技术，将液相色谱-质谱联用法的灵敏度提升了47倍。结果与结论：通过分析同一动物的微样本和常规样本，证实了稀疏采样得到的药代动力学特征可能无法全面代表个体动物的完整特征，这种偏差可能会通过增加或减少治疗效果的表观效应来影响测试结果。微采样技术相较于稀疏采样技术，能够提供无偏的结果。通过微流液相色谱-质谱联用技术，实现了在降低样本体积的同时，提升检测灵敏度的目标。