{"id":98087,"date":"2018-03-11T10:18:48","date_gmt":"2018-03-11T10:18:48","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/desarrollo-de-metodos-cromatograficos-y-de-analisis-por-inyeccion-en-flujo-para-la-caracterizacion-y-determinacion-de-farmacos-antirretrovirales\/"},"modified":"2018-03-11T10:18:48","modified_gmt":"2018-03-11T10:18:48","slug":"desarrollo-de-metodos-cromatograficos-y-de-analisis-por-inyeccion-en-flujo-para-la-caracterizacion-y-determinacion-de-farmacos-antirretrovirales","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/quimica-analitica\/desarrollo-de-metodos-cromatograficos-y-de-analisis-por-inyeccion-en-flujo-para-la-caracterizacion-y-determinacion-de-farmacos-antirretrovirales\/","title":{"rendered":"Desarrollo de m\u00e9todos cromatogr\u00e1ficos y de an\u00e1lisis por inyecci\u00f3n en flujo para la caracterizaci\u00f3n y determinaci\u00f3n de f\u00e1rmacos antirretrovirales"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Antonio Checa G\u00f3mez <\/strong><\/h2>\n<p>La terapia antirretroviral ha mejorado sustancialmente tanto la duraci\u00f3n como la calidad de vida de las personas infectadas por el virus de la inmunodeficiencia humana (vih). Durante los \u00faltimos 25 a\u00f1os, el estudio del mecanismo de infecci\u00f3n del virus, ha conducido a la aparici\u00f3n de f\u00e1rmacos clasificados en familias dependiendo de la etapa de infecci\u00f3n sobre la que act\u00faan.  la caracterizaci\u00f3n de estos analitos y la determinaci\u00f3n de sus concentraciones en diversas matrices, especialmente en plasma, permite optimizar el tratamiento recibido por los pacientes. Si los niveles en sangre son demasiado altos existe el riesgo de peligrosos efectos secundarios. Si por el contrario estos no llegan a las concentraciones requeridas, la efectividad frente al virus disminuye y aumenta la probabilidad del desarrollo de resistencias ante los f\u00e1rmacos. Para su monitorizaci\u00f3n terap\u00e9utica, dado el elevado n\u00famero de determinaciones a realizar, se requieren metodolog\u00edas anal\u00edticas que permitan determinar estas concentraciones de una forma r\u00e1pida, sencilla y lo m\u00e1s barata posible. en la presente memoria se presentan, en dos bloques, diferentes metodolog\u00edas para el control de las concentraciones en diferentes matrices de este tipo de compuestos.  el primer conjunto de m\u00e9todos est\u00e1 basado en an\u00e1lisis por inyecci\u00f3n en flujo (fia). Debido a la complejidad de las matrices, habitualmente se requiere un tratamiento previo de la muestra y una posterior separaci\u00f3n de los compuestos antes de proceder a su determinaci\u00f3n. En los procedimientos fia aqu\u00ed descritos, las medidas instrumentales se realizan con un detector de diodos en serie para obtener las se\u00f1ales sin previa separaci\u00f3n de los analitos, disminuyendo as\u00ed el tiempo de an\u00e1lisis a dos o tres minutos. Para el c\u00e1lculo de las concentraciones, los datos generados se tratan mediante resoluci\u00f3n multivariante de curvas basada en m\u00ednimos cuadrados alternos (mcr-als) y regresi\u00f3n por m\u00ednimos cuadrados parciales (pls). De esta manera se han podido cuantificar diversos inhibidores de la transcriptasa inversa en disoluciones acuosas, y muestras biol\u00f3gicas de plasma y orina.  para las matrices biol\u00f3gicas, los l\u00edmites detecci\u00f3n alcanzados han sido elevados y, por ello, se presentan un segundo bloque metodolog\u00edas basadas en cromatograf\u00eda de l\u00edquidos con detecci\u00f3n espectrofotom\u00e9trica ultravioleta (uv) o acoplada a espectrometr\u00eda de masas (ms) y masas en t\u00e1ndem (ms\/ms). el primero de estos m\u00e9todos cromatogr\u00e1ficos consiste en la separaci\u00f3n y determinaci\u00f3n de los f\u00e1rmacos de los inhibidores de la transcriptasa inversa an\u00e1logos de nucle\u00f3sidos (nrti), no an\u00e1logos de nucle\u00f3sidos (nnrti) y de la proteasa (pi), utilizando un tratamiento de muestra basado en extracci\u00f3n en fase s\u00f3lida empleando detecci\u00f3n uv. El tiempo de an\u00e1lisis es de 20 minutos, inferior a los tiempos presentados en otros estudios anteriores.  los tiempos de an\u00e1lisis mejoran con las metodolog\u00edas que utilizan detecci\u00f3n ms y ms\/ms. En este apartado, se presentan los trabajos realizados para la determinaci\u00f3n simult\u00e1nea de nrtis, nnrtis y pis, as\u00ed como una metodolog\u00eda r\u00e1pida para la determinaci\u00f3n de nnrtis y pis en suero, que se aplica en la monitorizaci\u00f3n terap\u00e9utica de los niveles sangu\u00edneos de estos f\u00e1rmacos en pacientes enfermos. como trabajo adicional, se presenta una revisi\u00f3n bibliogr\u00e1fica en la que se recogen los trabajos publicados en este campo durante los \u00faltimos cinco a\u00f1os.   aids therapy has substantially improved both life expectancy and quality of people infected by human inmunodeficience virus (hiv). Over the last 25 years, the study of the virus mechanisms of infection has led to the appearance of drugs, divided into families depending on the stage of viral infection that they act on. the characterization of these drugs and the determination of their concentrations, specially in plasma, allows the optimization of the medical treatment received by the patients. When blood levels are too high, dangerous side effects may appear. On the contrary, if these levels do not reach a minimum amount, the effectiveness of the drug is compromised and the probability of developing resistance is increased. Because of the large number of measures required in clinical analysis, new analytical methods that allow drug quantification in a fast, simple and inexpensive way are needed. in this doctoral thesis, different methodologies to quantify these compounds in biological matrices are presented  in two chapters. a first group of methods is based on flow injection analysis (fia). Due to the matrix complexity, sample pretreatment and compound separation prior to drug determination is often necessary. Fia methods here presented take advantage of data generated using a diode array detection so sample separation is not required and overall analysis time is decreased to 2 or 3 min. For concentration calculations, data generated is treated using multivariate curve resolution based on alternated least squares (mcr-als) and partial least squares regression (pls). This way allows drug quantification  of different reverse transcriptase inhibitors in synthetic mixtures and biological samples such as plasma and urine. limits of detection reached in these biological matrices were high and, thus, a second group of methodologies based on liquid chromatography (lc) with ultraviolet (uv) mass spectrometry (ms) and tandem mass spectrometry (ms\/ms) detection have been developed. the hplc-uv method allows the separation and quantification of drugs belonging to the nucleoside transcriptase reverse inhibitors (nrti), non nucleoside reverse transcriptase inhibitors (nnrti) and protease inhibitors (pi) families using sample solid phase extraction as a sample pretreatment. Total analysis time is 20 min. This is shorter than times presented in previous hplc-uv studies published in the literature. the analysis time improved when ms and ms\/ms detection are used. In the section of hplc-ms(\/ms) section, works for simultaneous determination of nrti, nnrti and pi drugs are described. A fast hplc-ms\/ms method for the simultaneous determination of nnrti and pi drugs in serum, which is applied in therapeutic drug monitoring, is also presented. as an additional work, a review dealing with works published during the last five years is presented.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Desarrollo de m\u00e9todos cromatogr\u00e1ficos y de an\u00e1lisis por inyecci\u00f3n en flujo para la caracterizaci\u00f3n y determinaci\u00f3n de f\u00e1rmacos antirretrovirales<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Desarrollo de m\u00e9todos cromatogr\u00e1ficos y de an\u00e1lisis por inyecci\u00f3n en flujo para la caracterizaci\u00f3n y determinaci\u00f3n de f\u00e1rmacos antirretrovirales <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Antonio Checa G\u00f3mez <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Barcelona<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 16\/12\/2009<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Santiago Hern\u00e1ndez Cassou<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: miquel Esteban cortada <\/li>\n<li>ludovic Duponchel (vocal)<\/li>\n<li>  (vocal)<\/li>\n<li>  (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Antonio Checa G\u00f3mez La terapia antirretroviral ha mejorado sustancialmente tanto la duraci\u00f3n como la calidad de vida [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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