Keywords
Diclofenac
Phytotherapeutic
Calendula officinalis
GC/MS
HPLC
LC/MS
Phytotherapeutic
Calendula officinalis
GC/MS
HPLC
LC/MS
How to Cite
Stashenko, E., González, A.-. F., Martínez, J.-. R., Durán, D.-. C., Oliveros, C.-. A., Gualteros, L.-. K., Salgar-Rangel, W., Henríquez, J.-. C., & Rojas, J.-. D. (2020). Finding of diclofenac in a marigold-based phytotherapeutic product commercialized in Colombia. Salud UIS, 52(3), 261–284. https://doi.org/10.18273/revsal.v52n3-2020008
Abstract
Introduction: The consultation of a person who brought a marigold-based phytotherapeutic product whose consumption caused strong adverse reactions, originated this investigation of the composition of this product. Objective: to characterize the chemical composition of samples of different lots of a commercial product called calendula-based phytotherapeutic product (Calendula officinalis) (PFC) commercialized in Colombia. Methodology: Tablets of eight packs of the phytotherapeutic product from four different production batches (2017 and 2018) were analyzed. Headspace analysis (HS) of tablets by solid phase microextraction (SPME) was carried out with a PDMS/ DVB fiber (65 µm), exposed to the HS of the sample for 30 min at 50 °C. Volatile fractions were analyzed by gas chromatography coupled to mass spectrometry (GC/MS). Tablet extracts obtained with methanol:water mixture (1:1, v / v) were analyzed by liquid chromatography (LC) of high (HPLC) and ultra-high performance (UHPLC) with diode array (DAD) and high-resolution mass spectrometric (HRMS) detectors, respectively; diclofenac was quantified by external calibration and standard addition. Low- and high-resolution mass spectra (MS, HRMS) and fragmentation patterns of detected substances were studied, using GC/HRTOF-MS and LC/HRMS-Orbitrap. Results: in tablets analyzed by HS-SPME, monoterpenoids and sesquiterpenoids of plant origin, phthalates, solvent residues (2-chloroethanol, ethylene glycol) and intermediary chemicals in diclofenac synthesis (2,6-dichloroaniline and 2,6- chloro-N-phenyl-benzenamine) were found. In the chromatograms (GC/MS) of the extracts of tablets obtained with organic solvent (dichloromethane), diclofenac, its impurities A, B and C, diclofenac esters, and some other compounds were detected; diclofenac quantification by HPLC found amounts of ca. 40 mg (7 - 8%) in tablets (> 70 analyzed) chosen at random from eight packs of the calendula-based phytotherapeutic product, purchased in the local market in Bucaramanga (Colombia). Conclusion: each analyzed tablet contained around 40 mg of the synthetic compound diclofenac (substance not declared in the product’s label) and no tablet contained detectable amounts of esters of the triterpenoids oleanane or faradiol, which are calendula extract constituents that possess antiinflammatory activity; a few flavonoids that are common to many plants were found in amounts a thousand times smaller than that of diclofenac.
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36. El Haj BM, Al Ainri AM, Hassan MH, Khadem RK, Marzouq MS. The GC/MS analysis of some commonly used non-steroidal anti-inflammatory drugs (NSAIDs) in pharmaceutical dosage forms and in urine. Forensic Sci Int, 1999; 105(3): 141-153. doi: https://doi.org/10.1016/S0379-0738(99)00106-1
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43. Blau K, Halket J (Editors). Handbook of Derivatives for Chromatography, Second Edition, Chichester, UK: John Wiley and Sons Ltd, 1993: 1-370.
44. Snow N (Editor). Basic Multidimensional Gas Chromatography, London, UK: Academic Press; 2020: 1-330.
45. Ramos L (Editor). Comprehensive Two-Dimensional Gas Chromatography. Amsterdam: Elsevier; 2009: 1-328.
46. López de Bustamante FM. Plantas medicinales y aromáticas. Estudio, cultivo y procesado. Madrid: Mundi-Prensa; 1987: 125-128.
47. Ministerio de la Protección Social. Vademécum colombiano de plantas medicinales. Bogotá, D.C., Colombia, 2008: 53-55.
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