Hallazgo de diclofenaco en un producto fitoterapéutico a base de caléndula comercializado en Colombia

Resumen

Introducción: la consulta de un particular que trajo un producto fitoterapéutico a base de caléndula cuyo consumo le causó fuertes reacciones adversas, originó esta investigación sobre la composición de este producto. Objetivo: caracterizar  la  composición  química  de  muestras  de  lotes  diferentes  de  un  producto comercial  denominado fitoterapéutico  a  base  de  caléndula (Calendula  officinalis) (PFC) comercializado  en  Colombia. Metodología: se analizaron tabletas de ocho cajas del PFC de cuatro lotes diferentes de producción (2017 y 2018). Se llevó a cabo el análisis de espacio de cabeza (HS) de tabletas por microextracción en fase sólida (SPME), con una fibra PDMS/DVB (65 μm), expuesta al HS de la muestra durante 30 min a 50 °C. Las fracciones volátiles se analizaron por cromatografía de gases acoplada a espectrometría de masas (GC/MS). Los extractos de tabletas obtenidos con mezcla de metanol:agua (1:1, v/v) se analizaron por cromatografía líquida (LC) de alta (HPLC) y ultra-alta eficiencia (UHPLC), con detectores de arreglo de diodos (DAD) y espectrometría de masas de alta resolución (HRMS), respectivamente; la  cuantificación  de  diclofenaco  se  hizo  por  calibración  con  patrón  externo  y  poradición de estándar. Los espectros de masas de baja y alta resolución y patrones de fragmentación de las sustancias detectadas se estudiaron, usando GC/HRMS y LC/HRMS-Orbitrap. Resultados: en tabletas analizadas por HS-SPME, se  encontraron  monoterpenoides  y  sesquiterpenoides  de  origen  vegetal,  ftalatos,  residuos  de  solventes (2-cloroetanol, etilenglicol) y sustancias químicas intermediarias en la síntesis de diclofenaco (2,6-dicloroanilina y  2,6-cloro-N-fenil-bencenamina).  En  los  cromatogramas,  obtenidos  por  GC/MS  de  los  extractos  de  tabletas obtenidos con diclorometano, se detectaron diclofenaco, sus impurezas A, B y C, los ésteres de diclofenaco y algunas  otras  impurezas.  Diclofenaco  en  cantidad  ca. 40 mg (7-8%) se cuantificó por HPLC en tabletas (> 70 analizadas) escogidas al azar de ocho cajas del PFC, adquirido en el mercado local de Bucaramanga (Colombia). Conclusión: en cada tableta analizada se determinaron alrededor de 40 mg del compuesto sintético diclofenaco (sustancia no declarada en la etiqueta del producto) y en ninguna se detectaron ésteres de los triterpenoides oleanano o faradiol, constituyentes del extracto de caléndula que poseen actividad antiinflamatoria; se encontraron algunos flavonoides comunes a muchas plantas, en cantidades mil veces menores que la de diclofenaco.

 

 

Palabras clave: Diclofenaco, Fitoterapéutico, Calendula officinalis, GC/MS, HPLC, LC/MS

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Publicado
2020-08-31
Sección
Artículos Científicos