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| Author(s): |
Bruna Cordeiro Santos de Moura
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Ribeirão Preto. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) |
| Defense date: | 2014-12-04 |
| Examining board members: |
Regina Helena Costa Queiroz;
Evandro José Cesarino;
Cristina Márcia Wolf Evangelista
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| Advisor: | Regina Helena Costa Queiroz |
| Abstract | |
Currently, the number of patients who are diagnosed with some form of depression, among them, major depressive disorder, increases considerably, either because of more accurate diagnosis or by the epidemiology of the disease. One should add the fact that many patients, despite the amount of types of antidepressants currently available for therapy are refractory to the treatment prescribed, because of the adverse effects appear, or their toxic effects, or by simply not observed improvement then the prescription. Therefore, new pharmacological treatments are available. To assist in maximum effectiveness in its use, this paper presents a methodology on HPLC for simultaneous determination of seven antidepressants, tricyclic and non-tricyclic, moclobemide, venlafaxine, citalopram, agomelatine, duloxetine, amitriptyline and sertraline in human plasma, later to be applied in monitoring depressed patients. The simple and accurate method of sample preparation consists of the liquid-liquid extraction with recovery between 73% to 86% (except for moclobemide, 55%). Separation was achieved using a reverse phase column Lichrospher® 60 RP-select B LiChroCART 4mm x 250mm, 5?m internal diameter, Merck, under isocratic conditions, with UV detection at 230nm, with a mobile phase consisting of a mixture of 35% acetonitrile:methanol 55/5 (v/v) and 65% 0.25M acetate buffer, pH 4.4. The standard curves were linear in the working range of 2,5-1000 ng/mL for moclobemide, 5-2000 ng/mL to venlafaxine, citalopram, agomelatine, duloxetine and amitriptyline and 10-2000ng/mL to sertraline. The intra and interassay precisions were performed at three concentrations (50, 200 and 500 ng/mL). The coefficients of variation for intra-assay precision were less than 8.6% for all compounds and the coefficients of variation for interassay precision were lower than 8.5%. The limits of quantification were 2.5 ng/mL for moclobemide, 5 ng/mL for venlafaxine, citalopram, duloxetine, agomelatine, amitriptyline and 10 ng/mL for sertraline. No interference of drugs normally associated with antidepressants was observed. The developed method was applied to the monitoring of 79 patients receiving prolonged treatment with amitriptyline, sertraline and venlafaxine. And, the plasma concentrations of healthy volunteer patients undergoing single dose agomelatine were evaluated. Therapeutic drug monitoring, is to ensure maximum clinical efficacy coupled with minimal adverse effects in patients undergoing long-term therapy is needed and to monitor adherence to treatment since depression is among the major causes of morbidity and social disability increasing prevalence estimate of 2030; characterized as one of the largest and most costly public health problems (AU) | |
| FAPESP's process: | 12/03706-9 - Threrapeutic drug monitoring of agomelatine, sertraline and venlafaxine in depressed patients. |
| Grantee: | Bruna Cordeiro Santos de Moura |
| Support Opportunities: | Scholarships in Brazil - Master |