通过体积吸收性微量采样进行药物监测：减轻血细胞比容影响的方法开发考量
Drug monitoring by volumetric absorptive microsampling: method development considerations to mitigate hematocrit effects.
作者信息
Fang Kasie, Bowen Chester L, Kellie John F, Karlinsey Molly Z, Evans Christopher A
机构信息
Bioanalysis, In-vitro/In-vivo Translation, Platform Technology & Science, GlaxoSmithKline Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA.
CRO RA CMC 4, R&D Chief Regulatory Office, GlaxoSmithKline Pharmaceuticals, 1250 S. Collegeville Rd, Collegeville, PA 19426, USA.
出版信息
Bioanalysis. 2018 Feb;10(4):241-255. doi: 10.4155/bio-2017-0221. Epub 2018 Jan 15.
AIM
GSKA is a compound that was in development in clinical trials. A bioanalysis method to quantify GSKA using volumetric absorptive microsampling (VAMS) was developed and hematocrit (HCT) related assay bias was investigated.
METHODOLOGY
After accurate sampling of 10 μl blood, VAMS tips were air dried approximately 18 h and desorbed by an aqueous solution containing internal standard. The recovered blood underwent liquid-liquid extraction in ethyl acetate to minimize matrix suppression. Assay accuracy, precision, linearity, carryover, selectivity, recovery, matrix effects, HCT effects and long-term quality control stability were evaluated.
CONCLUSION
HCT-related assay bias was minimized in 30-60% blood HCT range, and all validation parameters met acceptance criteria. The method is suitable for quantitative analysis of GSKA in human blood.
目的
GSKA是一种正在进行临床试验开发的化合物。开发了一种使用体积吸收微采样（VAMS）定量GSKA的生物分析方法，并研究了与血细胞比容（HCT）相关的测定偏差。
方法
准确采集10μl血液后，将VAMS吸头在空气中干燥约18小时，并用含有内标的水溶液解吸。回收的血液在乙酸乙酯中进行液液萃取，以尽量减少基质抑制。评估了测定的准确性、精密度、线性、残留、选择性、回收率、基质效应、HCT效应和长期质量控制稳定性。
结论
在30 - 60%血液HCT范围内，与HCT相关的测定偏差最小化，所有验证参数均符合验收标准。该方法适用于人血中GSKA的定量分析。
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