[Therapeutic equivalence evaluated by in vitro studies of multisource pharmaceutical products: case studies of amoxicillin, doxycycline and fluconazole in Lima, Peru]. / Equivalencia terapéutica evaluada mediante estudios in vitro de medicamentos multifuentes: estudio de casos de amoxicilina, doxiciclina y fluconazol en Lima, Perú.

The objective of the study was to determine the therapeutic equivalence evaluated through in vitro studies of four brands of drugs containing amoxicillin, doxycycline, and fluconazole purchased at pharmaceutical facilities in Metropolitan Lima, and to establish their interchangeability with a reference product (RP). A validated method of visible ultraviolet spectrophotometry was used to determine the dissolution profile. The similarity factor (f2) was used to establish the therapeutic equivalence, being considered equivalent if the values of f2 were between 50 and 100. For doxycycline, the four drugs were equivalent in vitro to the RP; for amoxicillin, only two drugs were equivalent in vitro to the RP; and for fluconazole, none was equivalent in vitro to the RP. It is concluded that some amoxicillin and fluconazole drugs circulating in the national market do not meet the therapeutic equivalence assessed by in vitro studies; in other words, they are not interchangeable.

El objetivo del estudio fue determinar la equivalencia terapéutica evaluada mediante estudios in vitro de cuatro marcas de medicamentos conteniendo amoxicilina, doxiciclina y fluconazol adquiridos en establecimientos farmacéuticos de Lima Metropolitana y establecer su intercambiabilidad con un producto de referencia (PR). Se empleó un método validado de espectrofotometría ultravioleta visible para determinar el perfil de disolución. El factor de similitud (f2) se utilizó para establecer la equivalencia terapéutica, considerándose equivalentes si los valores de f2 se encontraban entre 50 y 100. Para doxiciclina los cuatro medicamentos fueron equivalentes in vitro al PR, para amoxicilina sólo dos medicamentos fueron equivalentes in vitro al PR y para fluconazol ninguno fue equivalente in vitro al PR. Se concluye que algunos medicamentos de amoxicilina y fluconazol que circulan en el mercado nacional no cumplen con la equivalencia terapéutica evaluada mediante estudios in vitro; es decir, no son intercambiables.

Equivalencia terapéutica evaluada mediante estudios in vitro de medicamentos multifuentes: estudio de casos de amoxicilina, doxiciclina y fluconazol en Lima, Perú / Therapeutic equivalence evaluated by in vitro studies of multisource pharmaceutical products: case studies of amoxicillin, doxycycline and fluconazole in Lima, Peru

RESUMEN El objetivo del estudio fue determinar la equivalencia terapéutica evaluada mediante estudios in vitro de cuatro marcas de medicamentos conteniendo amoxicilina, doxiciclina y fluconazol adquiridos en establecimientos farmacéuticos de Lima Metropolitana y establecer su intercambiabilidad con un producto de referencia (PR). Se empleó un método validado de espectrofotometría ultravioleta visible para determinar el perfil de disolución. El factor de similitud (f2) se utilizó para establecer la equivalencia terapéutica, considerándose equivalentes si los valores de f2 se encontraban entre 50 y 100. Para doxiciclina los cuatro medicamentos fueron equivalentes in vitro al PR, para amoxicilina sólo dos medicamentos fueron equivalentes in vitro al PR y para fluconazol ninguno fue equivalente in vitro al PR. Se concluye que algunos medicamentos de amoxicilina y fluconazol que circulan en el mercado nacional no cumplen con la equivalencia terapéutica evaluada mediante estudios in vitro; es decir, no son intercambiables.

ABSTRACT The objective of the study was to determine the therapeutic equivalence evaluated through in vitro studies of four brands of drugs containing amoxicillin, doxycycline, and fluconazole purchased at pharmaceutical facilities in Metropolitan Lima, and to establish their interchangeability with a reference product (RP). A validated method of visible ultraviolet spectrophotometry was used to determine the dissolution profile. The similarity factor (f2) was used to establish the therapeutic equivalence, being considered equivalent if the values of f2 were between 50 and 100. For doxycycline, the four drugs were equivalent in vitro to the RP; for amoxicillin, only two drugs were equivalent in vitro to the RP; and for fluconazole, none was equivalent in vitro to the RP. It is concluded that some amoxicillin and fluconazole drugs circulating in the national market do not meet the therapeutic equivalence assessed by in vitro studies; in other words, they are not interchangeable.

[Validation of a liquid chromatography method for rifampicin determination in human plasma]. / Validación de un método de cromatografía líquida para la determinación de rifampicina en plasma humano.

OBJECTIVES: To validate the high-performance liquid chromatography method (HPLC) for rifampicin (RFP) determination in human plasma. MATERIALS AND METHODS: A HPLC method for RFP determination in plasma was developed. The separation was performed by reversed-phase chromatography with C18 column and a mobile phase composed of a mixture of acetonitrile and monobasic potassium phosphate buffer solution 0.05 M (38:62 v/v) at 335 nm in which standard rifampicin quinone (RFP-QN) was used. RESULTS: The retention times of RFP and RFP-QN were 7.81 and 12.26 minutes, respectively. The trial was linear from 0.5 to 250 ug/mL. The evaluated parameters of precision, accuracy, selectivity, linearity, and recovery complied with the established international standards for validation of bioanalytical methods. CONCLUSIONS: The developed HPLC method is simple, specific, sensitive, selective and linear for a wide range of RFP concentrations in plasma.

Validación de un método de cromatografía líquida para la determinación de rifampicina en plasma humano / Validation of a liquid chromatography method for rifampicin determination in human plasma

Objetivos: Validar un método de cromatografía líquida de alta resolución (HPLC) para la determinación de rifampicina (RFP) en plasma humano. Materiales y métodos. Se desarrolló un método HPLC para la determinación de RFP en plasma. La separación fue realizada por cromatografía de fase reversa con una columna C18 y una fase móvil compuesta por una mezcla de acetonitrilo y solución amortiguadora de fosfato de potasio monobásico 0,05 M (38:62 v/v) a 335 nm. En el cual se empleó como estándar interno rifampicina quinona (RFP-QN). Resultados. Los tiempos de retención de RFP y RFP-QN fueron 7,81 y 12,26 minutos, respectivamente. El ensayo fue lineal de 0,5 a 250 ug/mL Los parámetros evaluados de precisión, exactitud, selectividad, linealidad, recuperación cumplieron con lo establecido en las guías internacionales de validación de métodos bioanalíticos. Conclusiones. El método HPLC desarrollado es simple, específico, sensible, selectivo y lineal para un amplio rango de concentraciones de RFP en plasma.

Objectives: To validate the high-performance liquid chromatography method (HPLC) for rifampicin (RFP) determination in human plasma. Materials and methods. A HPLC method for RFP determination in plasma was developed. The separation was performed by reversed-phase chromatography with C18 column and a mobile phase composed of a mixture of acetonitrile and monobasic potassium phosphate buffer solution 0.05 M (38:62 v/v) at 335 nm in which standard rifampicin quinone (RFP-QN) was used. Results. The retention times of RFP and RFP-QN were 7.81 and 12.26 minutes, respectively. The trial was linear from 0.5 to 250 ug/mL. The evaluated parameters of precision, accuracy, selectivity, linearity, and recovery complied with the established international standards for validation of bioanalytical methods. Conclusions. The developed HPLC method is simple, specific, sensitive, selective and linear for a wide range of RFP concentrations in plasma.

Equivalencia terapéutica de tabletas de diazepam dispensadas en la ciudad de Ica, Perú / Therapeutic equivalency of tablets of diazepam dispended in the city of Ica, Peru

Objetivos: Determinar la equivalencia terapéutica in vitro de tres formulaciones de diazepam 10 mg tabletas, para establecer su intercambiabilidad con el medicamento de referencia original. Material y métodos: Estudio descriptivo, comparativo, realizado en junio del 2010, utilizando tres medicamentos genéricos dispensados en la ciudad de Ica y el medicamento original de referencia: Diazepam (Valium®) de laboratorios Roche. Se determinaron los perfiles de disolución efectuados en medios similares a pH fisiológicos del organismo según lo señalado por la OMS (Reporte Técnico 937). Para establecer la equivalencia terapéutica se empleó el factor de similitud (f2), considerando que dos formulaciones son equivalentes terapéuticos in vitro si los valores están comprendidos entre 50 y 100. Resultados: Los medicamentos evaluados presentaron a pH 1,2 una disolución muy rápida, sin embargo las tres formulaciones de prueba y el de referencia presentaron a pH 4,5 y pH 6,8 una disolución lenta con valores f2 a pH 4,5: Genérico A (f2 = 76,0); Genérico B (f2 = 68,9); Genérico C (f2 = 30,5); y a pH 6,8: Genérico A (f2 = 60,6); Genérico B (f2 = 78,2); Genérico C (f2 =20,4). Conclusiones: Según los valores f2 encontrados para las tres formulaciones de diazepam el medicamento genérico C (genérico nacional) no es equivalente al medicamento de referencia dado que no se pudo demostrar su intercambiabilidad, la que si se logró establecer para los medicamentos genéricos A y B.

Objectives: To determine the in-vitro therapeutic equivalence of three formulations of diazepam in tablets of 10mg to establish their interchangeability with the original brand name product. Methods: Descriptive and comparative study performed in September 2010 using three generic presentations dispended in the city of Ica compared to the original brand name product Diazepam (Valium®) from Roche Pharmaceutical Laboratories. We determined the dissolution profiles performed in similar media at physiologic pH based on WHO recommendations (Technical report 937). To establish therapeutic equivalence, we used the similarity factor (f2) and considered therapeutic equivalence if values were between 50 and 100. Results: All presentations had a very rapid dissolution at pH=1.2. However, the three generic presentations and the brand name product had slower dissolutions with f2 values at pH=4.5 of 76.0 for Generic A; 68.9 for Generic B; and 30.5 for Generic C, and f2 values at pH=6.8 of 60.6 for Generic A; 78.2 for Generic B and 20.4 for Generic C, respectively. Conclusions: Based on the f2 values found for the three generic presentations of diazepam, only the generic C presentation was not equivalent compared to the brand name product.

Estudio de bioequivalencia del ibuprofeno 400 mg tabletas / Bioquivalence study of ibuprofen 400 mg tablets

Objetivo. Determinar la biodisponibilidad de dos formulaciones de ibuprofeno 400mg tabletas, para establecer si el medicamento multifuente (genérico) es bioequivalente al de referencia (Motrin® 400mg). Materiales y métodos. Se diseñó un estudio abierto, randomizado, cruzado, dos periodos, con siete días de lavado, con 12 voluntarios sanos de ambos sexos, entre 21 y 48 años, quienes ingirieron una tableta del medicamento genérico o de referencia, según randomización, con 200mL de agua. Luego de ingerir el medicamento se colectó 4mL de sangre por voluntario para la cuantificación plasmática de ibuprofeno. Las muestras de plasma se analizaron por cromatografía líquida acoplada al espectrofotómetro de masas (LC-MS/MS) con ionización electrospray ión negativo, aplicando monitoreo de reacción selectiva. La bioequivalencia se determinó con los parámetros farmacocinéticos de área bajo la curva AUC(0-t), UC(0-∞) y concentración máxima (Cmax). Resultados. Según análisis estadístico, se encontraron: AUC multifuente(0-t) = 86,85 (μg*h)/mL, AUCRef.(0-t)= 81,20 (μg*h)/mL, AUCmultifuente(0-∞)= 88,67 (μg*h)/mL, AUCRef.(0-∞)= 82,83(μg*h)/mL, Cmáxmultifuente = 17,70 ug/mL, CmáxRef. =18,09 μg/mL, con rango de 0,93-1,24 para AUC(0-t), 0,93-1,24 para AUC(0-∞) y 0,81-1,19 para Cmax. Conclusión. Los valores encontrados de ibuprofeno están dentro de los requisitos de la OMS y la FDA, para establecer bioequivalencia (0,80û1,25), demostrándose que el ibuprofeno genérico es bioequivalente al de referencia en velocidad y cantidad de ibuprofeno absorbido en el organismo.

Objective. To determine the bioavailability of two dosage forms of ibuprofen 400mg tablets, for establishing if the multisource (generic) drug is bioequivalent to the reference (Motrin® 400mg tablets). Materials and methods. It was designed an opened study, randomized, two periods, cross over, and seven days washout period, with 12 healthy volunteers (male and female), between 21 and 48 years old, who have taken one tablet of the multisource or reference tablets; according to randomization; with 200 mL of water. After drug intake 4 mL of blood was collected from each volunteer, for quantification of ibuprofen. The plasma samples with ibuprofen and sodium diclofenac (internal standard) were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) with negative ion electrospray ionization using selected reaction monitoring. The bioequivalence was established with pharmacokinetics parameters: area under the curve AUC(0-t), AUC(0-∞) and maximum concentration (Cmax). Results. According to statistical analysis were founded: AUCmultisource(0-t) = 86.85 (ug*h)/mL, AUCRef.(0-t) = 81.20 (ug*h)/mL, AUCmultisource(0-∞) = 88.67 (ug*h)/mL, AUCRef.(0-∞) = 82.83 (ug*h)/mL, Cmáxmultisource = 17.70 ug/mL, CmáxRef.=18.09 ug/mL, with intervals of 0.93-1.24 for AUC(0-t), 0.93-1.24 for AUC(0-∞) and 0.81-1.19 for Cmax. Conclusions. The values founded for AUC(0-t), AUC(0-∞) and Cmax are within the established limits by WHO and FDA (0,80 -1,25), so ibuprofen 400mg tables; multisource drug, is bioequivalent to Motrin 400mg tablets, with regard to both the rate and extent of absorption.

Use of refractometry and colorimetry as field methods to rapidly assess antimalarial drug quality.

The proliferation of counterfeit and poor-quality drugs is a major public health problem; especially in developing countries lacking adequate resources to effectively monitor their prevalence. Simple and affordable field methods provide a practical means of rapidly monitoring drug quality in circumstances where more advanced techniques are not available. Therefore, we have evaluated refractometry, colorimetry and a technique combining both processes as simple and accurate field assays to rapidly test the quality of the commonly available antimalarial drugs; artesunate, chloroquine, quinine, and sulfadoxine. Method bias, sensitivity, specificity and accuracy relative to high-performance liquid chromatographic (HPLC) analysis of drugs collected in the Lao PDR were assessed for each technique. The HPLC method for each drug was evaluated in terms of assay variability and accuracy. The accuracy of the combined method ranged from 0.96 to 1.00 for artesunate tablets, chloroquine injectables, quinine capsules, and sulfadoxine tablets while the accuracy was 0.78 for enterically coated chloroquine tablets. These techniques provide a generally accurate, yet simple and affordable means to assess drug quality in resource-poor settings.