RESUMEN
This study investigates the oxidation of pharmaceuticals, endocrine disrupting compounds and pesticides during ozonation applied in drinking water treatment. In the first step, second-order rate constants for the reactions of selected compounds with molecular ozone (k(O3)) were determined in bench-scale experiments at pH 8.10: caffeine (650+/-22M(-1)s(-1)), progesterone (601+/-9M(-1)s(-1)), medroxyprogesterone (558+/-9M(-1)s(-1)), norethindrone (2215+/-76M(-1)s(-1)) and levonorgestrel (1427+/-62M(-1)s(-1)). Compared to phenolic estrogens (estrone, 17beta-estradiol, estriol and 17alpha-ethinylestradiol), the selected progestogen endocrine disruptors reacted far slower with ozone. In the second part of the study, bench-scale experiments were conducted with surface waters spiked with 16 target compounds to assess their oxidative removal using ozone and determine if bench-scale results would accurately predict full-scale removal data. Overall, the data provided evidence that ozone is effective for removing trace organic contaminants from water with ozone doses typically applied in drinking water treatment. Ozonation removed over 80% of caffeine, pharmaceuticals and endocrine disruptors within the CT value of about 2 mg min L(-1). As expected, pesticides were found to be the most recalcitrant compounds to oxidize. Caffeine can be used as an indicator compound to gauge the efficacy of ozone treatment.
Asunto(s)
Disruptores Endocrinos/química , Ozono/química , Plaguicidas/química , Preparaciones Farmacéuticas/química , Purificación del Agua/métodos , Abastecimiento de Agua/análisis , Cafeína/química , Cafeína/aislamiento & purificación , Disruptores Endocrinos/aislamiento & purificación , Estradiol/química , Estradiol/aislamiento & purificación , Estriol/química , Estriol/aislamiento & purificación , Estrógenos/química , Estrógenos/aislamiento & purificación , Estrona/química , Estrona/aislamiento & purificación , Concentración de Iones de Hidrógeno , Levonorgestrel/química , Levonorgestrel/aislamiento & purificación , Medroxiprogesterona/química , Medroxiprogesterona/aislamiento & purificación , Estructura Molecular , Noretindrona/química , Noretindrona/aislamiento & purificación , Oxidación-Reducción , Plaguicidas/aislamiento & purificación , Preparaciones Farmacéuticas/aislamiento & purificación , Progesterona/química , Progesterona/aislamiento & purificación , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/aislamiento & purificación , Abastecimiento de Agua/normasRESUMEN
A system is proposed for the classification of related organic impurities in drugs and drug products including among others (separated and non-separated) intermediates, various kinds of by-products, among them products of different side reactions, epimeric/diastereomeric, enantiomeric impurities, impurities in natural products, and finally degradation products. Examples are taken mainly from the author's own experience and from among the named impurities in the European Pharmacopoeia with focus on impurities in hydrocortisone, prednisolone, enalapril maleate, lisinopril, ethynodiol diacetate, pipecuronium bromide, cimetidine, and ethynylsteroids. The methodological aspects of impurity profiling from the detection to the identification/structure elucidation and quantitative determination of impurities are briefly summarized.
Asunto(s)
Contaminación de Medicamentos , Compuestos Orgánicos/análisis , Preparaciones Farmacéuticas/aislamiento & purificación , Cimetidina/química , Cimetidina/aislamiento & purificación , Enalapril/química , Enalapril/aislamiento & purificación , Diacetato de Etinodiol/química , Diacetato de Etinodiol/aislamiento & purificación , Hidrocortisona/química , Hidrocortisona/aislamiento & purificación , Lisinopril/química , Lisinopril/aislamiento & purificación , Noretindrona/química , Noretindrona/aislamiento & purificación , Norgestrel/química , Norgestrel/aislamiento & purificación , Preparaciones Farmacéuticas/química , Pipecuronio/química , Pipecuronio/aislamiento & purificación , Prednisolona/química , Prednisolona/aislamiento & purificaciónRESUMEN
4-Ene-3-ketosteroids and 17-ketosteroids were quantitatively transformed into the corresponding hydrazones using Girard P and T reagents, respectively. The positively charged derivatives were separated by capillary electrophoresis. The spectrophotometric characteristics of the derivatives permitted their sensitive detection in the 230-280 nm range. The steroids investigated included nortestosterone and its phenylpropionate, norethisterone and its oenanthate, d,l-norgestrel, dehydroepiandrosterone, androstenedione and ethisterone.
Asunto(s)
Cetosteroides/aislamiento & purificación , Androstenodiona/análogos & derivados , Androstenodiona/análisis , Androstenodiona/aislamiento & purificación , Betaína/análogos & derivados , Betaína/química , Deshidroepiandrosterona/análogos & derivados , Deshidroepiandrosterona/análisis , Deshidroepiandrosterona/aislamiento & purificación , Electroforesis Capilar , Etisterona/análogos & derivados , Etisterona/análisis , Etisterona/aislamiento & purificación , Indicadores y Reactivos/química , Cetosteroides/análisis , Nandrolona/análogos & derivados , Nandrolona/análisis , Nandrolona/aislamiento & purificación , Noretindrona/análogos & derivados , Noretindrona/análisis , Noretindrona/aislamiento & purificación , Norgestrel/análogos & derivados , Norgestrel/análisis , Norgestrel/aislamiento & purificación , Espectrofotometría UltravioletaRESUMEN
PIP: A method generally applicable to procedures for extraction and purification of ethynyl steroids in urine and plasma before gas chromatography (GC)/mass spectrometry (MS) analysis is described. The method requires using 20 ml of urine or 10 ml of plasma, which is then extracted on a column of Amberlite (3 gm). The extract is filtered to remove organic cations, and then after neutral steroids and other compounds are separated into groups by passing the efluent through the column, a further filtering on SP-Sephadex yields ethynyl steroids, which are selectively retained by the ion exchanger and are then eluted by displacement with l-hexyne. Using this method, recoveries of ethynyl steroids were from 75-90%. A simplified method is also outlined which can be used when separation of neutral, phenolic, and conjugated steroids is not required. The GC/MS analyses are performed using an OV-1 or SE-30 open tubular capillary column and single ion detection. A combination of external and internal standards is used. Limit of detection of unconjugated ethynylestradiol in urine was 5 pgm/ml. The paper concludes with examples of analyses of urine from a healthy woman taking 250 mcgm of (-)norgestrel and 50 mcgm of ethynylestradiol daily.^ieng
Asunto(s)
Etinilestradiol/aislamiento & purificación , Noretindrona/aislamiento & purificación , Norgestrel/aislamiento & purificación , Etinilestradiol/sangre , Etinilestradiol/orina , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Masculino , Noretindrona/sangre , Noretindrona/orina , Norgestrel/sangre , Norgestrel/orina , Fenoles/aislamiento & purificaciónAsunto(s)
Etinilestradiol/aislamiento & purificación , Diacetato de Etinodiol/aislamiento & purificación , Mestranol/aislamiento & purificación , Noretindrona/aislamiento & purificación , Noretinodrel/aislamiento & purificación , Animales , Radioisótopos de Carbono , Cromatografía de Gases , Cromatografía por Intercambio Iónico , Cromatografía en Capa Delgada , Perros , Espectrometría de Masas , Noretinodrel/metabolismo , Noretinodrel/orina , Plata , TritioAsunto(s)
Estradiol/metabolismo , Noretindrona/farmacología , Norgestrel/farmacología , Ovario/fisiología , Glándulas Suprarrenales/análisis , Animales , Castración , Cerebelo/análisis , Cromatografía de Gases , Estradiol/análisis , Estradiol/sangre , Femenino , Hipotálamo/análisis , Hígado/análisis , Noretindrona/aislamiento & purificación , Hipófisis/análisis , Ratas , Tritio , Útero/análisis , Vagina/análisisRESUMEN
PIP: A collaborative study of the analysis of mestranol in combination with norethindrone or norethynodrel by column chromatography and ultraviolet determination is presented. The study consisted of 4 samples which were a commercial norethindrone tablet, a synthetic norethindrone mixture, a commercial norethynodrel tablet, and a synthetic norethynodrel mixture. The samples were analyzed by 13 collaborators. Average mestranol recoveries were 100.4, 99.9, 98.7, and 101.2%, respectively.^ieng