The liquid chromatography tandem mass spectrometry method (LC-MS/MS) was used to determine the content of sibutramine (SB), N-desmethyl sibutramine (DSB) and N-didesmethyl sibutramine (DDSB) illegaly mixed in weight loss dietary supplements. Sibutramine and its derivatives were extracted by methanol; impurities in the extract were removed by graphitized carbon black (GCB) adsorbent. The chromatographic separation of analytes took place on C18 column (100 mm x 2.1 mm, 3.5 µm) with a gradient mobile phase of acetonitrile and 2 mM ammonium acetate in 0.1% formic acid solution. Multiple reaction monitoring (MRM) in the positive mode was used to detect and quantify SB, DSB and DDSB at m/z 279.9/124.8; 266.0/124.8 and 252.1/125.0, respectively. The method was validated following the AOAC requirements for specificity, repeatability and recovery. Calibration curves lineared from 0.002 to 0.1 µg/mL for SB, DSB and DDSB. The method was successfully applied to determine the content of SB, DSB and DDSB in weight loss dietary supplements that were randomly collected from phamacies in Hanoi of three formulations of hard capsule, soft capsule and teabag. The results shown that six samples had SB and DSB with the content in the range of 0.817 - 31.7 mg/g.
sibutramine, N-desmethyl sibutramine, N-didesmethyl sibutramine, weight lossdietary supplement, LC-MS/MS
[1] A. Krivohlavek, I. Žuntar, M. Ivešić, I. M. Andačić, S. Šikić, and M. Vrebčević, “Sibutramine in slimming food supplements on the Croatian market determined by validated highpressure liquid chromatographyelectrospray tandem mass spectrometry method”, Journal of Food and Nutrition Research, vol. 55, pp. 222228, 2016.
[2] E. P. Gueorguieva, K. Ivanov, S. Gueorguiev, A. Mihaylova, V. Madzharov and S. Ivanova, “Detection of sibutramine in herbal food supplements by UHPLC/HRMS and UHPLC/MSMS”,Biomedical Research, vol. 29, no.14, pp. 30063009, 2018
[3] H. M. Yano, F. F. Farias, M. B. D. Bianco and L. M. Trujllo, “Determination of the Sibutramine Content of Dietary Supplements Using LCESIMS/MS”, Journal of Pharmaceutical Analysis. 32 (8): 11641169, 2013.
[4] V. S. Ponnuru, B.R. Challa and R. Nadendla, “Quantification of sibutramine and its two metabolites in human plasma by LCESI MS/MS and its application in a bioequivalence study”, Journal of Pharmaceutical Analysis, vol. 2, no. 4, pp. 249257, 2012.
[5] P. Zou, S. SY. Oh, K.H. Kiang, MY. Low and B.C. Bloodworth, “Detection of sibutramine, its two metabolites and one analogue in a herbal product for weight loss by liquid chromatography triple quadrupole mass spectrometry and timeofflight mass spectrometry”, Rapid Communications in Mass Spectrometry, vol. 21, no. 4, pp. 614618, 2007.
[6] J. Wang, B. Chen and S. Yao, “Analysis of six synthetic adulterants in herbal weightreducing dietary supplements by LC electrospray ionizationMS”, Food Additives & Contaminants: Part A, vol. 25, no. 7, pp. 822830, 2008.
[7] J. Chen, W. Lu, Q. Zhang and X. Jiang, “Determination of the active metabolite of sibutramine by liquid chromatographyelectrospray ionization tandem mass spectrometry”, Journal of Chromatography B, vol. 785, pp. 197203, 2003.
[8] S. H. Roh, Y.P. Kang, S. Park, Y. Huh, J. Lee, J.H. Park, D. Kim and S.W. Kwon, “Determination of tadalafil and Ndesmethylsibutramine in health and dietary supplements using ultraperformance liquid chromatography (UPLC) coupled with quadrupoletimeofflight mass spectrometry (QTOF MS)”, Food Additives and Contaminants, vol. 28, no. 11, pp. 14751482, 2011.
[9] E. Ariburnu, M. F. Uludag, H. Yalcinkaya and E. Yesilada, “Comparative determination of sibutramine as an adulterant in natural slimming product by HPLC and HPTLC densitometry”, Journal of Pharmaceutical and Biomedical Analysis, vol. 6465, pp. 7781, 2012.
[10] Z. Huang, S. Xiao, D. Luo, Bo Chen and S. Yao, “Simultaneous Determination of Sibutramine and NDidesmethylsibutramine in Dietary Supplements for Weight Control by HPLCESIMS”, Journal of Chromatographic Science, vol. 46, no. 8, pp. 707711, 2008.
[11] M. Chorilli, R. Bonfilio, R. S. Chicarelli and H. R. N. Salgado, “Development and validation of an analytical method by PRHPLC for quantification of sibutramine in pharmaceutical capsule”, Analytical Methods, vol. 3, pp. 985990, 2011.
[12] Y. Chena, L. Zhaob, F. Lua, Y. Yuc, Y. Chaia and Y. Wua, “Determination of synthetic drugs used to adulterate botanical dietary supplements using QTRAP LCMS/MS”, Food Additives and Contaminants, vol. 26, no. 5, pp. 595603, 2009.
[13] F. V. Sardela, M. T. R. Motta, M. C. Padilha, H. M. G. Pereira and F. R. Aquino Neto, “Analysis of sibutramine metabolites as Ntrifluoroacetamide and Otrimethylsilyl derivatives by gas chromatographymass spectrometry in urine”, Journal of Chromatogr B, vol. 877, no. 27, pp. 30033011, 2009.
[14] S. StranoRossi, C. Colamonici and F. Botre, “Detection of sibutramine administration: a gas chromatography/mass spectrometry study of the main urinary metabolites”, Rapid Communication in Mass Spectrometrometry, vol. 21, no. 2, pp. 7988, 2007.
[15] P. Zou, S. SY. Oh, KH. Kiang, MY. Low and B. C. Bloodword, “Detection of sibutramine,its two metabolites and one analogue in a herbal product for weight loss by liquid chromatography triple quadrupole mass spectrometry and timeofflight mass spectrometry”, Rapid Communication in Mass Spectrometrometry, vol. 21, pp. 614618, 2007.
[16] N. T. Luyện, “Xác định chất cấm Sibutramine trong thực phẩm chức năng giảm béo bằng phương pháp HPLC”, Luận văn Thạc sỹ, Đại học Quốc gia Hà Nội, Việt Nam, 2014.
[17] T. Kamadi, I. Fidrianny, Amirmusadad, “Development of analytical method for identification of sibutramine in traditional medicine using solid phase extraction: high performance liquid chromatography”, Asian Journal of Pharmaceutical and Clinical Research, vol 9, no. 6, pp. 201209, 2016.