ABSTRACT
As intoxicações por medicamentos são predominantes no Brasil e frequentes na faixa etária de 0 a 14 anos. O ácido valproico (AV) vem se destacando em virtude do aumento do seu espectro de utilização na terapêutica clínica, porém, a hepatotoxicidade pode ser desencadeada por altas concentrações desse fármaco, apresentando alta incidência em crianças. Logo, tornam-se importantes métodos rápidos de quantificação desse fármaco, a fim de auxiliar o clínico no tratamento da intoxicação. Diante desse cenário, os objetivos deste trabalho foram comparar metodologias analíticas para quantificação de AV por CLAE-F (fluorescência) e CG/DIC (detecção por ionização de chama) em relação à sua potencial aplicação em toxicologia clínico-laboratorial de urgência. Para quantificação de AV por fluorescência, realizou-se a derivatização do AV com 4-(Bromometil)-7-metoxicumarina, sendo o produto da reação analisado em λ de emissão de 325 e detecção de 398 nm, na faixa de calibração de 1-300miug/mL. Com relação à CG/DIC, esta apresentou-se linear na faixa de 100-2000 miug/mL, sem necessidade de derivatização prévia. A técnica de CG/DIC mostrou-se mais apropriada para análises toxicológicas de urgência em casos de intoxicação com AV, tendo em vista o menor tempo de corrida, a linearidade obtida, menor custo, rapidez e praticidade, além de utilizar um equipamento robusto, disponível na grande maioria dos laboratórios de toxicologia de pequeno e médio porte.
Poisoning by drugs is rather frequent in Brazil in the age range of 0 to 14 years. Intoxication by valproic acid (VA) stands out because of an increase in its spectrum of clinical use; hepatotoxicity is an important reaction that can be triggered by high concentrations of this drug and there is a high incidence of toxic events in children. Therefore, fast methods of analysing this drug are essential, in order to help the clinician to treat the intoxication. Given this scenario, the objective of this study was to compare analytical methods to determine VA, by HPLC-F (fluorescence) and GC/FID (flame ionization detection), assessing their potential application in the urgent toxicology clinic. For the fluorometric analysis, the VA was first derivatized with 4-bromomethyl-6, 7-dimethoxycoumarin, and the resulting compound was excited at λ = 325 nm and detected by the emission at 398 nm. The calibration range was 1-300 miug/mL. The GC/FID method showed a linear response in the range 100-2000 miug/mL, without requiring prior derivatization. The technique of GC/FID proved more appropriate for the urgent toxicological analysis of VA, in view of the shorter time of analysis, linearity, lower cost, speed, efficiency and the use of robust equipment that is already available in the great majority of small and medium-sized toxicological clinics.
Subject(s)
Fluorescence , Poisoning , Valproic Acid , Flame IonizationABSTRACT
Dopamine constitutes about 80 percent of the content of central catecholamines and has a crucial role in the etiology of several neuropsychiatric disorders, including Parkinson's disease, depression and schizophrenia. Several dopaminergic drugs are used to treat these pathologies, but many problems are attributed to these therapies. Within this context, the search for new more efficient dopaminergic agents with less adverse effects represents a vast research field. The aim of the present study was to report the structural design of two N-phenylpiperazine derivatives, compound 4: 1-[1-(4-chlorophenyl)-1H-4-pyrazolylmethyl]-4-phenylhexahydropyrazine and compound 5: 1-[1-(4-chlorophenyl)-1H-1,2,3-triazol-4-ylmethyl]-4-phenylhexahydropyrazine, planned to be dopamine ligands, and their dopaminergic action profile. The two compounds were assayed (dose range of 15-40 mg/kg) in three experimental models: 1) blockade of amphetamine (30 mg/kg, ip)-induced stereotypy in rats; 2) the catalepsy test in mice, and 3) apomorphine (1 mg/kg, ip)-induced hypothermia in mice. Both derivatives induced cataleptic behavior (40 mg/kg, ip) and a hypothermic response (30 mg/kg, ip) which was not prevented by haloperidol (0.5 mg/kg, ip). Compound 5 (30 mg/kg, ip) also presented a synergistic hypothermic effect with apomorphine (1 mg/kg, ip). Only compound 4 (30 mg/kg, ip) significantly blocked the amphetamine-induced stereotypy in rats. The N-phenylpiperazine derivatives 4 and 5 seem to have a peculiar profile of action on dopaminergic functions. On the basis of the results of catalepsy and amphetamine-induced stereotypy, the compounds demonstrated an inhibitory effect on dopaminergic behaviors. However, their hypothermic effect is compatible with the stimulation of dopaminergic function which seems not to be mediated by D2/D3 receptors