將PEG 400從血漿中去除的主要目的就是為了清除可能引發的離子抑制效應。圖5為由下面方程式得出的基質效應數據一覽,據最新AAPS論文報道6。

基質效應 =(含PEG的峰響應值/不含PEG的峰響應值)
圖表A所示數據來源于經Oasis
MCX萃取去除PEG的血漿樣品。圖表B所示數據來源于經萃取后又加入PEG的血漿樣品,可以看到在樣品制備過程中未去除PEG的結果。由圖顯示,若未去除PEG,醋丁洛爾和美托洛爾受到嚴重的離子抑制作用影響,基質效應因子分別為0.45和0.77。由上述數據可以清晰看出,那些與PEG峰共流出的分析物,使用Oasis
MCX SPE板去除PEG后,離子抑制效應能得以有效清除。經PEG去除后,最終醋丁洛爾和美托洛爾的基質效應因子分別為0.93和1.04。
結論
Oasis MCX
96孔板提供了一種用于去除血漿樣品中高濃度PEG的簡便、快捷、高效的方法,從而消除早期藥代動力學研究中常見的基質效應(通常是離子抑制效應)。此外,該解決方案無需進行色譜分析方法的再開發、樣品的稀釋、及其他費時費力的流程即可成功解決上述問題,這使得整個解決方案廣泛適用于高通量分析的應用。
參考文獻
1. Tong X, Wang J,
Zheng S, Pivnichny J, Griffin P, Shen X, Donnelly M, Vakerich K, Nunes
C, and Fenyk-Melody J. Effect of signal interference from dosing
excipients on pharmacokinetic screening of drug candidates by liquid
chromatography/mass spectrometry. Anal Chem 2002 74:6305-6313.
2.
Weaver R and Riley R. Identification and reduction of ion suppression
effects on pharmacokinetic parameters by polyethylene glycol 400. Rapid
Comm Mass Spec 2006 20:2559-2564.
3. Shou W and Naidong W.
Post-column infusion stude of the ‘dosing vehicle effect’ in the liquid
chromatography/tandem mass spectrometric analysis of discovery
pharmacokinetic samples. Rapid Comm. Mass Spec 2003 17:589-597.
4.
Temesi D, Law B, and Howe N. Synthesis and evaluation of PEG414, a novel
formulating agent that avoids analytical problems associated with
polydispersive vehicles such as PEG400. J. Pharmaceutical Sciences 2003
92(12):2512-2518.
5. Larger P, Breda M, Fraier D, Hughes H, and James
C. Ion-suppression effects in liquid chromatography-tandem mass
spectrometry due to a formulation agent, a case study in drug discovery
bioanalysis. J. Pharm. Biomed. Anal. 2005 39:206-216.
6. Bansal S and
DeStefano A. Key elements of bioanalytical method development
validation for small molecules. T he AAPS Journal 2007 9(1):E109-E114