Cantú Marcelo Delmar, Toso Daniel Rodrigo, Lacerda Cristina Alves, Lanças Fernando Mauro, Carrilho Emanuel, Queiroz Maria Eugênia Costa
Instituto de Química de São Carlos, Universidade de São Paulo, Trabalhador São Carlense Avenue, 400-CEP: 13566-590 São Carlos, SP, Brazil.
Anal Bioanal Chem. 2006 Sep;386(2):256-63. doi: 10.1007/s00216-006-0629-5. Epub 2006 Jul 29.
Simple, sensitive, and reproducible off-line solid-phase microextraction and liquid chromatography (SPME/LC) methods are described for the determination of seven anticonvulsants and tricyclic antidepressants in human plasma. Factorial design and simplex methodology were applied in the optimization of the SPME procedure for tricyclic antidepressants analyses. Important factors in the SPME efficiency are discussed, such as the fiber coatings (both lab-made and commercial), extraction time, pH, ionic strength, influence of plasma proteins, and desorption conditions. The development of the lab-made fiber coatings, namely, octadecylsilane, aminosilane, and polyurethane, are further described and applied to anticonvulsants analyses. The investigated plasmatic range for the evaluated anticonvulsants, using CW-TPR fiber, were the following: phenylethylmalonamide (3.00-40.0 microg mL(-1)), phenobarbital (5.00-40.0 microg mL(-1)), primidone (3.00-40.0 microg mL(-1)), carbamazepine and carbamazepine-epoxide (2.00-24.0 microg mL(-1)), phenytoin (2.00-40.0 microg mL(-1)), and lamotrigine (0.50-12.0 microg mL(-1)). The antidepressants' linear plasmatic concentration ranged from 75.0 to 500 ng mL(-1) for imipramine, amitriptyline, and desipramine, and from 50.0 to 500 ng mL(-1) for nortriptyline, being in all cases, the limit of quantification represented by the lowest value. The precision (interassays) for all investigated drugs in plasma sample spiked with different concentrations of each analyte and submitted to the described procedures were lower than 15%. The off-line SPME/LC methodologies developed allow anticonvulsants and antidepressants analyses from therapeutic to toxic levels for therapeutic drug monitoring.
本文描述了一种简单、灵敏且可重复的离线固相微萃取和液相色谱法（SPME/LC），用于测定人血浆中的七种抗惊厥药和三环类抗抑郁药。在三环类抗抑郁药分析的SPME程序优化中应用了析因设计和单纯形法。讨论了SPME效率的重要影响因素，如纤维涂层（自制和商用）、萃取时间、pH值、离子强度、血浆蛋白的影响以及解吸条件。进一步描述了自制纤维涂层（即十八烷基硅烷、氨基硅烷和聚氨酯）的研制，并将其应用于抗惊厥药分析。使用CW-TPR纤维时，所评估的抗惊厥药的血浆检测范围如下：苯乙基丙二酰胺（3.00 - 40.0 μg mL⁻¹）、苯巴比妥（5.00 - 40.0 μg mL⁻¹）、扑米酮（3.00 - 40.0 μg mL⁻¹）、卡马西平和卡马西平环氧化物（2.00 - 24.0 μg mL⁻¹）、苯妥英（2.00 - 40.0 μg mL⁻¹）和拉莫三嗪（0.50 - 12.0 μg mL⁻¹）。对于丙咪嗪、阿米替林和地昔帕明，抗抑郁药的线性血浆浓度范围为75.0至500 ng mL⁻¹，对于去甲替林为50.0至500 ng mL⁻¹，在所有情况下，定量限均为最低值。在添加了不同浓度各分析物的血浆样品中，按照所述程序进行检测，所有研究药物的精密度（批间）均低于15%。所开发的离线SPME/LC方法可用于抗惊厥药和抗抑郁药从治疗水平到中毒水平的分析，以进行治疗药物监测。
