Chassaing C, Stokes J, Venn R F, Lanza F, Sellergren B, Holmberg A, Berggren C
Christophe Chassaing, Bioanalytical Group, Drug Metabolism, IPC 664, Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK.
J Chromatogr B Analyt Technol Biomed Life Sci. 2004 May 5;804(1):71-81. doi: 10.1016/j.jchromb.2003.12.011.
The use of molecularly imprinted polymers (MIPs) as sorbents for the solid phase extraction (SPE) of a pharmaceutical compound in development, prior to quantitative analysis was investigated. Three MIPs were synthesised using a structural analogue as the template molecule. Each polymer was prepared with different monomers and porogens. The MIPs were then tested for their performance both in organic and aqueous environments, the final aim being to load plasma directly onto the polymers. At an early development stage, there is a limited amount of compound available. Due to this limitation, reducing the amount of template required for imprinting was investigated. A MIP capable of extracting the analyte directly from plasma was produced. The specificity of the polymer allowed the method to be validated at a lower sensitivity than a more conventional SPE assay. For the first time, MIPs were packed into 96-well blocks enabling high throughput analysis. The analytical method was fully validated for imprecision and inaccuracy down to 4 ng/ml in plasma.
研究了在定量分析之前，使用分子印迹聚合物（MIP）作为吸附剂，对一种处于研发阶段的药物化合物进行固相萃取（SPE）。使用一种结构类似物作为模板分子合成了三种MIP。每种聚合物都用不同的单体和致孔剂制备。然后测试了这些MIP在有机和水性环境中的性能，最终目标是将血浆直接加载到聚合物上。在早期研发阶段，可用的化合物量有限。由于这一限制，研究了减少印迹所需模板量的方法。制备出了一种能够直接从血浆中提取分析物的MIP。该聚合物的特异性使得该方法能够在比传统SPE分析更低的灵敏度下进行验证。首次将MIP填充到96孔板中，实现高通量分析。该分析方法在血浆中低至4 ng/ml的精密度和准确度方面得到了充分验证。
