Identification and Quantification by HPLCDAD of Furosemide as a Co-adulterant in Products of Natural Origin


  • Centro Universitário Saúde ABC/ Faculdade de Medicina do ABC, Laboratório de Análises Clínicas, Brazil
  • Universidade Federal de São Paulo, Departamento de Ciências Farmacêuticas da, Brazil


The low cost added to easy access and expectation of low or no side effects make these products increasingly attractive. When a product of natural origin contains synthetic substances that are not declared in its formulation, the synthetic substance is characterized as adulteration. In order to identify and quantify adulterants in natural products, analytical methods have been developed and used as fundamental tools in the control of these products. Thus, two products of natural origin indicated for treatment of rheumatic and inflammatory diseases were analyzed to verify the presence of the co-adulterant furosemide. Co-adulterant presence in the products was tested using an Agilent® brand 1100 HPLC system with a quaternary pump, an automatic injector and a DAD detector, with a mobile phase composed of methanol/formic acid 0.2% 60/40 (v/v). HPLC-DAD indicates the presence of the undeclared furosemide compound in the original formulation of both analyzed samples. In sample A, 24 mg of furosemide per gram was found, while in sample B, 47mg per gram of product was obtained. The consumption of adulterated products may lead to risks such as drug interaction and intoxication, since active ingredients of synthetic origin are added without taking in consideration adjustments and quality of the raw material.


Chromatography, Co-Adulterant, Furosemide, HPLC, Natural Products

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Bast A, Chandler RF, Choy PC, Delmulle LM, Gruenwald J, Halkes SBA, et al. Botanical health products, positioning and requirements for effective and safe use. Environ. Toxicol. Pharmacol. 2002; 12:195–211. S1382-6689(02)00035-2

Giraldi M, Hanazaki N. Uso e conhecimento tradicional de plantas medicinais no Sertão do Ribeirão, Florianópolis, SC, Brasil. Acta Bot. Bras 2010; 24(2):395–406.

Pinto AC, Silva DHS, Bolzani VS, Lopes NP, Epifanio RA. Produtos naturais: atualidade, desafios e perspectivas. Quim. Nova. 2002; 25(1):45–61. S0100-40422002000800009

Barnes PM, Bloom B, Nahin RL. Complementary and alternative medicine use among adults and children: United States.National Health Statistics Report. 2002; 12:1–23.

Jung J, Hermanns-Clausen M, Weinmann W. Anorectic sibutramine detected in a Chinese herbal drug for weight loss. Forensic Science International. 2006; 161:221–2. PMid:16870382

Carvalho LM, Martini M, Moreira AP, Lima AP, Correia D, Falcão T, et al. Presence of synthetic pharmaceuticals as adulterants in slimming phytotherapeutic formulations and their analytical determination. Forensic Science International. 2011; 204:6–12. Mid:20554134

Doménech-Carbó A, Martini M, Carvalho LM, Viana C, Doménech-Carbóc MT, Silvac M. Screening of pharmacologic adulterant classes in herbal formulations using voltammetry of microparticles. Journal of Pharmaceutical and Biomedical Analysis. 2013; 74:194–204. PMid:23245251

Bhagavathula AS, Elnour AA, Shehab A. Pharmacovigilance on sexual enhancing herbal supplements. Saudi Pharmaceutical Journal. 2016; 24(1):115–8. PMid:26903775 PMCid:PMC4720019

Ching CK, Chen SLP, Lee HHC, Lam YH, Ng SW, Chen ML, et al. Adulteration of proprietary Chinese medicines and health products with undeclared drugs: experience of a tertiary toxicology laboratory in Hong Kong. British Journal of Clinical Pharmacology. 2018; 84:172–8. PMid:28965348 PMCid:PMC5736835

Ariburnu E, Uludag MF, Yalcinkaya H, Yesiladaa E. Comparative determination of sibutramine as an adulterant in natural slimming products by HPLC and HPTLC densitometry. Journal of Pharmaceutical and Biomedical Analysis. 2012; 64–65:77–81. PMid:22410500

Deconinck E, Sacré PY, Courselle P, Beer JO. Chromatography in the detection and characterization of illegal pharmaceutical preparations. Journal of Chromatographic Science. 2013; 51(8):791–806. https:// PMid:23377647

Bogusz MJ, Hassan H, Al-enazi E, Ibrahim Z, Al-Tufail M. Application of LC - ESI - MS - MS for detection of synthetic adulterants in herbal remedies. Journal of Pharmaceutical and Biomedical Analysis. 2006; 41:554–64. PMid:16427237

Calahan J, Howard D, Ahmad AJ, Gupta MP, Calderón AI. Chemical adulterants in herbal medicinal products: A Review.Planta Medica. 2016; 82:505–15. PMid:27054916

Cianchino V, Costa G, Ortega C, Martinez DL, Gomez RM.Analysis of potential adulteration in herbal medicines and dietary supplements for the weight control by capillary electrophoresis. Gomez Food Chemistry. 2008; 108:1075– 81. PMid:26065773

Wolfender JL. HPLC in natural product analysis: the detection issue. Planta Medica. 2009; 75(7):719–34. https:// PMid:19145552

Anvisa. Agência Nacional de Vigilância Sanitária, Brasil, Ministério da Saúde, Resolução RDC nº 166 de 25 de julho de 2017[Internet]. [cited 2018 Jul 16]. Available from: RDC_166_2017_COMP.pdf/d5fb92b3-6c6b-4130-8670-4e3263763401.

Ekar T, Kreft S. Common risks of adulterated and mislabeled herbal preparations. Food and Chemical Toxicology. 2019; 123:288–97. PMid:30339960

Chong YK, Ching CK, Ng SW, Mak TW. Corticosteroid adulteration in proprietary Chinese medicines: a recurring problem. Hong Kong Medical Journal. 2015; 21(5):411–16.

Mount DB. Thick ascending limb of the loop of Henle. Clinical Journal of the American Society of Nephrology. 2014; 9(11):1974–86. CJN.04480413. PMid: 25318757. PMCid:PMC4220766

Shankar SS, Brater DC. Loop diuretics: from the Na-K2Cl transporter to clinical use. American Journal of Physiology-Renal Physiology. 2003; 284(1):F11–21. ht tps://


Park HJ, Cho SH, Lee JH, Hwang IS, Han MK, et al. Screening for corticosteroid adulterants in Korean herbal medicines. Journal of Forensic Sciences. 2016; 61(1):226–9. PMid:26346959

Kennedy DA, Lupattelli A, Koren G, Nordeng H. Safety classification of herbal medicines used in pregnancy in a multinational study. BMC Complementary and Alternative Medicine. 2016;16:102. PMid:26980526. PMCid:PMC4793610

Bruno LO, Simoes RS, Simoes MJ, Girão MJBC, Grundmann O. Pregnancy and herbal medicines: An unnecessary risk for women’s health-A narrative review. Phytotherapy Research. 2018; 32(5):796–810. ptr.6020. PMid:29417644


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