血浆和全血抗凝剂抗衡离子的选择对生物分析过程中药物稳定性和基质效应的影响

Impact of plasma and whole-blood anticoagulant counter ion choice on drug stability and matrix effects during bioanalysis.

作者信息

Bergeron Mélanie, Bergeron Annik, Furtado Milton, Garofolo Fabio

机构信息

Algorithme Pharma Inc., 575 Armand-Frappier, Laval, Quebec, H7V 4B3, Canada.

出版信息

Bioanalysis. 2009 Jun;1(3):537-48. doi: 10.4155/bio.09.74.

DOI:10.4155/bio.09.74

PMID:21083151

Abstract

BACKGROUND

Anticoagulants are used to prevent coagulation in blood samples. The plasma pH may change with a different counter ion and anticoagulant; thus, it is essential to determine effects on drug stability and the matrix effect during the bioanalytical method development.

RESULTS

Cross-validation of multiple compounds between different counter ions was performed and no impact from the counter ion nature was demonstrated. Moreover, plasma stabilities and matrix effects for both fluconazole and granisetron were investigated thoroughly in numerous counter ions/anticoagulants (K(3)ethylenediaminetetraacetic acid [K(3)EDTA], K(2)EDTA, NaEDTA, NaHeparin and LiHeparin). Sirolimus, a large cyclic molecule, was also tested in different whole-blood EDTA counter ions. Results showed percentage deviation less than 8.5% and percentage cross-validation less than 8.4%.

CONCLUSION

None of the compounds tested had an impact on the matrix stabilities and matrix effect.

摘要

背景

抗凝剂用于防止血样凝固。血浆pH值可能会因不同的抗衡离子和抗凝剂而改变；因此，在生物分析方法开发过程中确定其对药物稳定性和基质效应的影响至关重要。

结果

对不同抗衡离子之间的多种化合物进行了交叉验证，未显示抗衡离子性质有任何影响。此外，在多种抗衡离子/抗凝剂（乙二胺四乙酸三钾[K₃EDTA]、乙二胺四乙酸二钾[K₂EDTA]、乙二胺四乙酸钠[NaEDTA]、钠肝素和锂肝素）中全面研究了氟康唑和格拉司琼的血浆稳定性和基质效应。西罗莫司是一种大环分子，也在不同的全血EDTA抗衡离子中进行了测试。结果显示偏差百分比小于8.5%，交叉验证百分比小于8.4%。