Optimization of solid-phase microextraction procedures for the determination of tricyclic antidepressants and anticonvulsants in plasma samples by liquid chromatography.
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.
Cantú
Marcelo Delmar
MD
Instituto de Química de São Carlos, Universidade de São Paulo, Trabalhador São Carlense Avenue, 400-CEP: 13566-590 São Carlos, SP, Brazil.
Toso
Daniel Rodrigo
DR
Lacerda
Cristina Alves
CA
Lanças
Fernando Mauro
FM
Carrilho
Emanuel
E
Queiroz
Maria Eugênia Costa
ME
D000639:Amitriptyline / Q000097:blood; D000927:Anticonvulsants / Q000097:blood*; D000929:Antidepressive Agents, Tricyclic / Q000097:blood*; D002220:Carbamazepine / Q000097:blood; D002853:Chromatography, Liquid / Q000379:methods*; D003891:Desipramine / Q000097:blood; D004852:Epoxy Compounds / Q000097:blood; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007099:Imipramine / Q000097:blood; D000077213:Lamotrigine; D009661:Nortriptyline / Q000097:blood; D010634:Phenobarbital / Q000097:blood; D010657:Phenylethylmalonamide / Q000097:blood; D011140:Polyurethanes / Q000737:chemistry; D011324:Primidone / Q000097:blood; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012821:Silanes / Q000737:chemistry; D013997:Time Factors; D014227:Triazines / Q000097:blood
D000927:Anticonvulsants; D000929:Antidepressive Agents, Tricyclic; D004852:Epoxy Compounds; D011140:Polyurethanes; D012821:Silanes; D014227:Triazines; D011324:Primidone; D000639:Amitriptyline; C024779:octadecylsilane; D002220:Carbamazepine; D010657:Phenylethylmalonamide; D009661:Nortriptyline; D007099:Imipramine; D003891:Desipramine; D000077213:Lamotrigine; D010634:Phenobarbital