Measuring VACV and ACV in Mouse and Human Plasma
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Pharmacokinetic (PK) studies can be challenging at times, especially when performed on mice where biological sample volumes are limited by things like the size of the animal. New research, recently published in the Journal of Chromatography B, looks at finding a way to create a highly-sensitive assay to measure the prodrug valacyclovir (VACV) as well as its metabolite, acyclovir (ACV) in both mouse and human plasma samples of limited volume.
Working with Limited Volumes
When it comes to drug discovery and development, pre-clinical pharmacokinetic studies use mouse models most frequently (among animal models). Because a mouse is physically small with a limited volume of biological fluid available, many studies will use composite blood sampling. With this method, a data point is collected from multiple mice, which allows for a sufficient aggregate volume to be collected but can sometimes create complications (like inter-animal variabilities), and requires more animal and material usage in general.
Developing a Highly-Sensitive Assay
To overcome these challenges, the researchers wanted to create a highly-sensitive assay for the target compound that would require a much smaller sample. Not only would this allow for a PK profile from one unique mouse, but would also allow the same strategy to be applied to other studies where the available volume of a blood sample may be limited.
Prior to this study, existing LC-MS/MS methods to quantify VACV and ACV in plasma needed a rather large sample volume (in one such study, the sample volume measured 250ul).
Smaller Sample Volumes Confirmed
The researchers were able to develop and validate a method by which they were able to accurately analyze VACV and ACV in small volumes of mouse plasma, requiring a plasma sample size of only 10ul. This method was applicable to a mouse PK study, and would also make a promising method for human PK studies - especially in circumstances where the sample volume may be a limiting factor - for example, in pediatrics and/or neonatal applications.
Further Reading & References:
A sensitive liquid chromatography-tandem mass spectrometry method for the quantification of valacyclovir and its metabolite acyclovir in mouse and human plasma. Jian Shi, Yongjun Hu, David E. Smith, Hao-Jie Zhu. Journal of Chromatogrpahy B (2018). https://doi.org/10.1016/j.jchromb.2018.06.040
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