Musteata Florin Marcel, de Lannoy Inés, Gien Brad, Pawliszyn Janusz
School of Pharmacy, Memorial University of Newfoundland, St. John's, NL, Canada.
J Pharm Biomed Anal. 2008 Aug 5;47(4-5):907-12. doi: 10.1016/j.jpba.2008.03.028. Epub 2008 Apr 8.
Pharmacokinetic (PK) studies in rats typically involve removal of serial blood samples following dosing. This research illustrates the development of a fast in vivo microextraction technique that has the potential to partly replace current sampling techniques based on blood draws, especially in the case of small animals.
The proposed sampling procedure is based on solid phase microextraction (SPME), an approach that has continued to revolutionize sampling and sample preparation ever since its discovery a decade ago. In vivo microextraction is faster than conventional methods, interferes minimally with the investigated system, minimizes errors associated with sample preparation and limits exposure of lab personnel to hazardous biological samples.
Here we show the successful application of fast microextraction during a full PK study with diazepam in rats. The results were found to correlate very well with a standard analytical method. Three calibration strategies--external, standard on the fiber, and double extraction--were employed to correlate the amount extracted with the in vivo concentration.
Our results demonstrate the unique advantages of this technique and highlight its utility as a valuable new tool for fast bioanalysis in support of in vivo sampling and PK studies, particularly during the early drug discovery process. This approach can be used not only for drugs, but also for other exogenous or endogenous compounds.
大鼠的药代动力学（PK）研究通常涉及给药后采集系列血样。本研究阐述了一种快速体内微萃取技术的开发，该技术有可能部分取代当前基于采血的采样技术，尤其是在小动物的情况下。
所提出的采样程序基于固相微萃取（SPME），自十年前发现以来，该方法一直在彻底改变采样和样品制备。体内微萃取比传统方法更快，对被研究系统的干扰最小，将与样品制备相关的误差降至最低，并限制实验室人员接触危险生物样品。
在此我们展示了快速微萃取在大鼠地西泮全药代动力学研究中的成功应用。结果发现与标准分析方法相关性非常好。采用了三种校准策略——外部校准、纤维上标准物校准和双重萃取——以使萃取量与体内浓度相关联。
我们的结果证明了该技术的独特优势，并突出了其作为快速生物分析的有价值新工具的实用性，以支持体内采样和药代动力学研究，特别是在早期药物发现过程中。这种方法不仅可用于药物，还可用于其他外源性或内源性化合物。
