Li Wenkui, Doherty John, Favara Sarah, Breen Christopher, Flarakos Jimmy, Tse Francis L S
Department of Drug Metabolism and Pharmacokinetics, Novartis Institutes for Biomedical Research, One Health Plaza, East Hanover, NJ 07936, USA.
Department of Drug Metabolism and Pharmacokinetics, Novartis Institutes for Biomedical Research, One Health Plaza, East Hanover, NJ 07936, USA.
J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Jun 1;991:46-52. doi: 10.1016/j.jchromb.2015.03.026. Epub 2015 Apr 3.
Quantitative bioanalysis of dried plasma spots (DPS) is not subject to the impact of hematocrit and sample non-homogeneity that are often encountered in dried blood spot (DBS) assay. In the present report, an evaluation of plasma microsampling for DPS has been conducted for the first time using ritonavir as a model compound orally administered to dogs. For this evaluation, an LC-MS/MS method was developed and validated according to the current health authorities' guidance and industry practice for the analysis of ritonavir in DPS samples. The measured ritonavir concentrations in the DPS samples prepared using SAFE-TEC devices and directly from the conventional wet plasma using standard pipette were compared with each other and against those of conventional wet plasma. Both DPS results correlated well with each other and were comparable to those of the wet plasma. Good incurred sample reanalysis results were obtained for the two sets of DPS samples and wet plasma as well. The current plasma microsampling for DPS can serve as an alternative to DPS sampling via standard pipetting and wet plasma in in vivo studies.
干血浆斑(DPS)的定量生物分析不受血细胞比容和干血斑(DBS)分析中经常遇到的样品不均匀性的影响。在本报告中,首次以利托那韦作为口服给犬的模型化合物,对用于DPS的血浆微量采样进行了评估。为了进行该评估,根据当前卫生当局的指导和行业惯例,开发并验证了一种用于分析DPS样品中利托那韦的液相色谱-串联质谱(LC-MS/MS)方法。将使用SAFE-TEC装置制备的DPS样品中测得的利托那韦浓度与使用标准移液器直接从常规湿血浆中测得的浓度进行了相互比较,并与常规湿血浆的浓度进行了比较。两种DPS结果相互之间相关性良好,并且与湿血浆的结果相当。两组DPS样品和湿血浆也都获得了良好的加标样品重新分析结果。目前用于DPS的血浆微量采样可作为体内研究中通过标准移液器采样和湿血浆采样的替代方法。