Cyproheptadine is an H1 antihistamine, that is often illegally added in dietary supplements to stimulate appetite and gain weight in children, currently banned for use in health supplements according to the provisions of Circular 10/2021-BYT. The method was using the Agilent Triple Quadrupole 6460 with fragments 288.1 → 96.1 and 288.1 → 191.2 selected for quantitative and qualitative. The separation was carried out on XBridge C18 column (100 mm × 2.1 mm, 3.5 µm) with a mobile phase consisting of acetonitrile and 0,1% formic acid. The analyte was extracted with methanol and cleaned up by d-SPE technique using a mixture of PSA and C18 powder. The recovery was in the range of 80-110%, the accuracy met the requirements of AOAC for method validation at spiked concentrations on three matrices of dietary supplements (granules, syrup, and powdered milk). Limits of detection and quantification were achieved at 0.08 mg/kg and 0.25 mg/kg with the syrup; 0.15 mg/kg and 0.50 mg/kg with granule and powdered milk samples. The method has been applied to analyze 30 samples and detected cyproheptadine in a syrup sample at 1.67 mg/dose of 10 mL. This method can be applied to analyzing cyproheptadine in dietary supplements on the market as well as developing for simultaneous determination of other adulterants with similar properties and effects in our next studies.
Cyproheptadine, H1 anti-histamine, dietary supplements, LC-MS/MS.
[1]. M. K. Church, M. Maurer, F. E. Simons et al., Risk of first-generation H(1)-antihistamines: a GA(2)LEN position paper, Allergy, vol. 65, no. 4, pp. 459-66, 2010.
[2]. S. Madani, O. Cortes, R. Thomas, "Cyproheptadin Use in Children With Functional Gastrointestinal Disorders," Journal of Pediatric Gastroenterology and Nutrition, vol. 62, no. 3, pp. 409-413, 2016.
[3]. Food and Drug Administration Philippines, FDA Advisory No. 2020-1271, Public Health Warning Against the Purchase and Use of the Following Unregistered Drug Products, 2020.
[4]. Ministry of Health (Vietnam), Circular 10/2021/TT-BYT Prescribing nomenclature list of agents prohibited from production and business of health protection food, 2021.
[5]. Sayann, T. Veeraiah, C. Reddy, "Determination of Cyproheptadine hydrochloride in Pure and Pharmaceutical forms: A Spectrophotometric study," Oriental Journal of Chemistry, nol. 31, no. 3, pp. 1779-1786, 2015.
[6]. Pan Li, Cuifeng Yang, Beibei Liu, "Sensitive Immunochromatographic Assay Using Highly Luminescent Quantum Dot Nanobeads as Tracer for the Detection of Cyproheptadine Hydrochloride in Animal-Derived Food," Frontiers in Chemistry, vol. 8, no. 575, pp. 1-11, 2020.
[7]. P. T. T. Tuyen, "Developing a method to identify some anti-allergy drugs illegally mixed in oriental medicinal products by LC-MS/MS," Master's thesis in pharmacy, Hanoi University of Pharmacy, 2019 (in Vietnamese).
[8]. V. S. Nguyen, H. D. Le, "Validation of LC-MS/MS method for determination of cyproheptadine in dietary supplements," Journal of Food and Nutrition Sciences, vol. 18, no. 2E, pp. 9-15, 2022.
[9]. J. A. Do, J. Kim, J. Choi et al., "Development of a LC-MS/MS method for simultaneous analysis of 20 antihistamines in dietary supplements," Analytical Science and Technology, vol. 28, pp. 86-97, 2015.
[10]. J. Kim, J. Choi, C. Yoon et al., "LC-MS/MS monitoring of 22 illegal antihistamine compounds in health food products from the Korean market," Journal of the Korean Society for Applied Biological Chemistry, vol. 58, pp. 137-147, 2015.
[11]. T. C. Son, Method validation and measurement uncertainty assessment in chemical analysis, Science and Technics Publishing House, 2021 (in Vietnamese).
[12]. AOAC Official Method 2007.01, Pesticide Residues in Foods by Acetonitrile Extraction and Partitioning with Magnesium Sulfate, 2007.