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Advisor(s)
Abstract(s)
Os casos de depressĆ£o tĆŖm vindo a aumentar cada vez mais. Muitas vezes por falta de
diagnĆ³stico atempado o tratamento inicial nĆ£o Ć© eficaz, o que faz com que o nĆŗmero de
doentes crĆ³nicos continue a aumentar, aumentando consequentemente o consumo
deste tipo de medicamentos. Em Portugal, os dados publicados pela Autoridade
Nacional do Medicamento e Produtos de SaĆŗde I.P. (INFARMED) referem que o
subgrupo farmacoterapĆŖutico antidepressivos e psicotrĆ³picos estava, em 2000, entre os
10 primeiros no que diz respeito aos encargos para o ServiƧo Nacional de SaĆŗde.
A prescriĆ§Ć£o dos antidepressivos de nova geraĆ§Ć£o, como os inibidores selectivos da
recaptaĆ§Ć£o da serotonina, tem sido crescente nos Ćŗltimos anos, jĆ” que apresentam
menos toxicidade para o organismo e um menor nĆŗmero de efeitos secundĆ”rios. No
entanto, nem sempre esta medicaĆ§Ć£o Ć© eficaz, continuando assim a prescrever-se
antidepressivos tricĆclicos e inibidores da monoaminoxidase, que apresentam uma
elevada toxicidade e sĆ£o muitas vezes usados em actos suicidas.
O objectivo a que nos propusemos com este trabalho foi desenvolver e comparar vƔrias
tĆ©cnicas para a preparaĆ§Ć£o de amostras, como a extracĆ§Ć£o lĆquido-lĆquido (LLE) e a
extracĆ§Ć£o em fase sĆ³lida (SPE), usando diferentes solventes e tipos de enchimento para a detecĆ§Ć£o de antidepressivos em plasma e urina. Os extractos foram analisados por
cromatografia lĆquida de alta eficiĆŖncia (HPLC) acoplada a um detector de fotodiodos
(PDA).
Foram estudados nove antidepressivos: amitriptilina, nortriptilina, clomipramina,
dotiepina, mianserina, trazodona, fluoxetina, sertralina e protriptilina, tendo sido este
Ćŗltimo usado como padrĆ£o interno.Os parĆ¢metros estudados foram a selectividade, recuperaĆ§Ć£o e limites de detecĆ§Ć£o,
tendo estes parĆ¢metros sido avaliados de acordo com as normas internacionalmente
aceites para a validaĆ§Ć£o de mĆ©todos bioanalĆticos.
Os valores de recuperaĆ§Ć£o obtidos situaram-se entre 16-82% para a LLE e 42-97% para
a SPE. De um modo geral, as tƩcnicas de SPE utilizadas demonstraram ser mais
adequadas para a determinaĆ§Ć£o deste tipo de compostos em fluidos biolĆ³gicos, devido
Ć presenƧa de um nĆŗmero menor de interferĆŖncias endĆ³genas. Por outro lado, a
simplicidade de execuĆ§Ć£o desta tĆ©cnica torna-a mais facilmente automatizĆ”vel.
Finalmente, foi ainda possĆvel demonstrar que o tipo de equipamento analĆtico
utilizado no decorrer deste trabalho (HPLC/PDA) Ć© uma tĆ©cnica Ćŗtil e ao alcance de
qualquer laboratĆ³rio para uma primeira fase da optimizaĆ§Ć£o de processos extractivos,
reservando-se tƩcnicas mais dispendiosas [como por exemplo LC/MS (MS) ou
UPLC/MS (MS)] para a posterior validaĆ§Ć£o dos mĆ©todos analĆticos desenvolvidos.
Depression situations are increasing every year. Initial treatment measures are often non-effective, and this can be due to the lack of an early diagnosis, leading to an increase in the number of patients with chronic disease. As a consequence, the consumption of antidepressant drugs also increases. In Portugal, and according to the published data by Autoridade Nacional do Medicamento e Produtos de SaĆŗde I.P. (INFARMED) referring to the year 2000, antidepressant and psychotropic medicines were included in the top 10 of the most burdensome therapeutic groups to the public treasury. The prescription of new generation antidepressants, such as the selective inhibitors of serotonin reuptake, has increased in recent years, as these are less toxic and present fewer side effects. However, this class of drugs is not always effective, thus tricyclic antidepressants and is monoaminoxidase inhibitors are still being largely prescribed; the toxicity of these drugs is high, and they are often used in suicides. The objective of this work was the development and comparison of several techniques for sample preparation, such as liquid-liquid extraction (LLE) or solid-phase extraction (SPE), for the detection of nine selected antidepressants in plasma and urine. Several different solvents and SPE cartridges (and sorbents) have been used, and extracts were analysed by high performance liquid chromatography (HPLC) coupled to a photodiode array detector (PDA). We have studied nine antidepressants, and these were amitriptyline, nortryptiline, clomipramine, dothiepin, mianserine, trazodone, fluoxetine, sertraline and protriptyline (internal standard). The studied parameters included selectivity, absolute recovery and detection limits, and these were evaluated taking into account internationally accepted criteria for bioanalytical method validation. The obtained recovery values were between 16-82% for LLE and 42-97% for SPE. In general, SPE-based techniques have shown more suitability for the determination of such compounds in these biological fluids due to the presence of less endogenous interferences. Moreover, this technique is more easily automated. Finally, it was further possible to demonstrate that the instrumentation used in this study (HPLC/PDA) is an useful and accessible analytical tool to any laboratory for the first stage of optimization of extraction methods, reserving more expensive techniques [e.g. LC/MS (MS) or UPLC/MS (MS)] for the subsequent validation of the developed analytical methods.
Depression situations are increasing every year. Initial treatment measures are often non-effective, and this can be due to the lack of an early diagnosis, leading to an increase in the number of patients with chronic disease. As a consequence, the consumption of antidepressant drugs also increases. In Portugal, and according to the published data by Autoridade Nacional do Medicamento e Produtos de SaĆŗde I.P. (INFARMED) referring to the year 2000, antidepressant and psychotropic medicines were included in the top 10 of the most burdensome therapeutic groups to the public treasury. The prescription of new generation antidepressants, such as the selective inhibitors of serotonin reuptake, has increased in recent years, as these are less toxic and present fewer side effects. However, this class of drugs is not always effective, thus tricyclic antidepressants and is monoaminoxidase inhibitors are still being largely prescribed; the toxicity of these drugs is high, and they are often used in suicides. The objective of this work was the development and comparison of several techniques for sample preparation, such as liquid-liquid extraction (LLE) or solid-phase extraction (SPE), for the detection of nine selected antidepressants in plasma and urine. Several different solvents and SPE cartridges (and sorbents) have been used, and extracts were analysed by high performance liquid chromatography (HPLC) coupled to a photodiode array detector (PDA). We have studied nine antidepressants, and these were amitriptyline, nortryptiline, clomipramine, dothiepin, mianserine, trazodone, fluoxetine, sertraline and protriptyline (internal standard). The studied parameters included selectivity, absolute recovery and detection limits, and these were evaluated taking into account internationally accepted criteria for bioanalytical method validation. The obtained recovery values were between 16-82% for LLE and 42-97% for SPE. In general, SPE-based techniques have shown more suitability for the determination of such compounds in these biological fluids due to the presence of less endogenous interferences. Moreover, this technique is more easily automated. Finally, it was further possible to demonstrate that the instrumentation used in this study (HPLC/PDA) is an useful and accessible analytical tool to any laboratory for the first stage of optimization of extraction methods, reserving more expensive techniques [e.g. LC/MS (MS) or UPLC/MS (MS)] for the subsequent validation of the developed analytical methods.
Description
Keywords
Serotonina Noradrenalina Antidepressivos tricĆclicos
Citation
Publisher
Universidade da Beira Interior