Pharmaceutical Analysis Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Student Research Committee, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Daru. 2020 Dec;28(2):615-624. doi: 10.1007/s40199-020-00366-5. Epub 2020 Aug 15.
Electromembrane extraction is a new membrane-based extraction method in which charged compounds are extracted by an electric field. So far, this method has been used to extract and isolate a variety of acidic and basic drugs from various samples, including blood and plasma. However, in this procedure, it is not yet clear whether only unbound fraction of a drug is extracted or the total drug. The aim of this study is to reveal the nature of drug extraction in the presence of plasma proteins.
To determine the nature of the extraction, the electromembrane extraction was performed from plasma solutions of phenytoin with concentrations 0.03 and 1.0 μg/mL, then the result was compared with the values obtained from the electromembrane extraction of ultrafiltrate of the same solutions (free concentration) and protein-free ultrafiltrate of plasma with final concentration of 0.03 and 1.0 μg/mL (total concentration). For this purpose, EME followed by capillary electrophoresis coupled with diode array detection was optimized and validated.
The results showed that the electromembrane extraction method was only able to extract the unbound fraction of phenytoin from plasma samples. The method was validated over a concentration range of 0.03-4 μg/mL. The inter and intra-assay precisions were less than 6.7%. The phenytoin protein binding was also determined to be in agreement with the literature data and confirms the validity of this method.
This sensitive and quick EME approach for determining the free concentration of a phenytoin, can be a good alternative to classic methods for therapeutic drug monitoring and pharmacokinetic studies.
电膜萃取是一种新型的基于膜的萃取方法，其中带电化合物通过电场进行萃取。到目前为止，这种方法已被用于从各种样品（包括血液和血浆）中提取和分离各种酸性和碱性药物。然而，在这个过程中，尚不清楚提取的是药物的游离部分还是总药物。本研究的目的是揭示在存在血浆蛋白的情况下药物萃取的性质。
为了确定萃取的性质，用电膜萃取法从浓度为 0.03 和 1.0μg/mL 的苯妥英血浆溶液中进行萃取，然后将结果与从相同溶液的超滤物（游离浓度）和无蛋白的血浆超滤物（最终浓度为 0.03 和 1.0μg/mL）（总浓度）进行电膜萃取所得到的值进行比较。为此，优化并验证了 EME 后与二极管阵列检测相结合的毛细管电泳。
结果表明，电膜萃取方法只能从血浆样品中提取苯妥英的游离部分。该方法在 0.03-4μg/mL 的浓度范围内进行了验证。日内和日间精密度均小于 6.7%。苯妥英蛋白结合也与文献数据一致，证实了该方法的有效性。
这种灵敏快速的 EME 方法可用于测定苯妥英的游离浓度，可作为经典的治疗药物监测和药代动力学研究方法的良好替代方法。
