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In this paper, a time-based multicommutated flow system is proposed for appropriate selection and modulation of mobile phase composition in flow-injection (FI)/sequential-injection (SI) chromatography. The novel flow assembly involves the on-line coupling of a short monolithic reversed-phase chromatographic column with a multisyringe flow injection set-up furnished with a set of solenoid valves. The proposed hyphenated technique was applied to the simultaneous spectrophotometric determination of thiamine (B(1)), pyridoxine (B(6)) and cyanocobalamin (B(12)) which were taken as model analytes. The separation method capitalizes on a dual isocratic elution protocol involving the use of a single forward stroke of the multisyringe pump for initial delivery of 50 mmol L(-1) ammonium acetate (pH 7.0) for 2.4 min followed by 50 mmol L(-1) ammonium acetate-methanol (80:20, v/v) for 6.4 min at 0.5 mL min(-1) and room temperature. Detection was performed at the maximum wavelength for each target vitamin-280 nm for B(1), 325 nm for B(6), and 360 nm for B(12). A first-order, two-level full-factorial design was utilized to ascertain the significant variables influencing the chromatographic separation and the magnitude of the interaction effects. The experimental design method revealed that resolution of the target vitamins is highly dependent on the pH, percentage of organic modifier, and their second-order interaction. The multisyringe flow-injection-based monolithic column separation method, which should be viewed as an expeditious and cost-effective alternative to the high-performance liquid chromatography counterpart, was applied to the separation and determination of B(1), B(6), and B(12) in different pharmaceutical dosage forms in less than 9 min. Statistical comparison of the results from the proposed procedure with those from the HPLC method endorsed by the US Pharmacopeia revealed there were no significant differences at the 95% confidence level.

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INTRODUCCIÓNLa hepatotoxicidad inducida por fármacos es una de las etiologías más comunes de hepatitis aguda en nuestro medio y representa la causa más frecuente de fallo hepático fulminante en EE. UU. (1). Sin embargo, las tasas reales de hepatitis secundaria a fármacos son desconocidas (2). La expresión clínica de estos cuadros es muy variable, oscilando entre alteraciones asintomáticas de las enzimas hepáticas hasta fallo hepático agudo fulminante y su diagnóstico precisa de un alto índice de sospecha y se sustenta en una correcta anamnesis y la exclusión de las causas más comunes potencialmente responsables (3,4 RESUMENLas reacciones adversas hepáticas relacionadas con la administración de fármacos (hepatotoxicidad) son cuadros relativamente frecuentes que presentan una amplia variabilidad clínica e histoló-gica. La identificación precoz de estos cuadros es fundamental en la práctica clínica debido a su potencial gravedad. En la mayoría de los casos la suspensión del fármaco desencadenante es suficiente para la resolución del cuadro clínico.A pesar de que los esteroides son utilizados en una amplia variedad de situaciones clínicas, la notificación de cuadros de hepatotoxicidad secundaria a esteroides intravenosos es excepcional.Presentamos el caso clínico de una mujer diagnosticada de esclerosis múltiple, que recibió metilprednisolona a altas dosis en forma de "pulsos" intravenosos como tratamiento de las reagudizaciones de su enfermedad y presentó 3 brotes recurrentes de hepatitis de predominio hepatocelular con un patrón clínico, analíti-co e histológico compatible con toxicidad hepática aguda secundaria a metilprednisolona intravenosa. En el tercer episodio se realizó una biopsia hepática que demostró un patrón de hepatitis aguda con necrosis líticas confluentes, histología no descrita previamente en pacientes tratados con esteroides intravenosos.Palabras clave: Metilprednisolona. Hepatotoxicidad. Esclerosis múltiple. ABSTRACTAdverse drug reactions (hepatotoxicity) are a frequent cause of acute liver injury with a wide clinical and histological spectrum. An early recognition of drug-related liver disease has been considered essential in clinical practice due to potential risks. In most cases exposure discontinuation improves the clinical picture.Steroids are used in a variety of clinical settings. However, intravenous steroids have rarely been associated with hepatotoxicity. We report the case of a middle-aged woman with multiple sclerosis who received a bolus of methylprednisolone on three occasions for the management of relapsing disease, with the development of repeated episodes of elevated liver enzymes after corticoid administration. In the third episode a liver biopsy was performed, which showed acute hepatitis with bridging necrosis; such histological picture has not been described before in patients treated with intravenous steroids.

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