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Current Pharmaceutical Analysis

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ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

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Clinical Trial

Application of an LC-MS/MS Method to a Urinary Excretion Study of Triflusal and its Main Metabolite 2-hydroxy-4-trifluoromethyl Benzoic Acid in Human Urine

Author(s): Jie Ge, Jin-Wen Wang, Qi-Yan Guo and Ai-Dong Wen*

Volume 16, Issue 3, 2020

Page: [328 - 334] Pages: 7

DOI: 10.2174/1573412914666181105125225

Price: $65

Abstract

Objective: A validated liquid chromatography-tandem mass spectrometry method (LCMS/ MS) was established to simultaneously determine the concentration of triflusal and its main metabolite 2-hydroxy-4-trifluoromethyl benzoic acid(HTB) in human urine.

Methods: The separation was performed on a Dikma C18 column using isocratic elution with acetonitrile-4 mmol/L ammonium acetate aqueous solution containing 0.3 % formic acid water (78: 28, V/V). The method involved extraction with methanol using protein precipitation. The precursor-toproduct ion transitions with multiple reaction monitoring was m/z 247.1→161.1, 204.8→106.7and 136.9→93.0 for triflusal, HTB and salicylic acid(IS), respectively. The method showed good linear relationships over the ranges of 0.08 to 48 μg/mL and0.5 to 50 μg/mL.

Results: It was the first time that a urinary excretion study of triflusal capsule as oral. The cumulative urinary recovery showed 8.5% and 2.7% for triflusal and HTB, respectively.

Conclusion: This method was successfully used for evaluating the pharmacokinetic properties of triflusal and HTB in urine in Chinese healthy subjects.

Keywords: Triflusal, HTB, method, determine, analysis, urine.

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[1]
McNeely, W.; Goa, K.L. Triflusal. Drugs, 1998, 55(6), 823-833.
[http://dx.doi.org/10.2165/00003495-199855060-00011] [PMID: 9617597]
[2]
Garcia Rafanell, J.; Planas, J.M.; Puig-Parellada, P. Comparison of the inhibitory effects of acetylsalicylic acid and trifusal on enzymes related to thrombosis. Arch. Int. Pharmacodyn. Ther., 1979, 237(2), 343-350.
[PMID: 226020]
[3]
Dominguez, M.J.; Vacas, M.; Sáez, Y.; Olabarría, I.; Velasco, A.; Iriarte, J.A.; Forn, J. Effects of triflusal in patients with prosthetic heart valves. Clin. Ther., 1985, 7(3), 357-360.
[PMID: 3838919]
[4]
de la Cruz, J.P.; Pavia, J.; Bellido, I.; González, M.C.; Sánchez de la Cuesta, F. Platelet antiaggregatory effect of triflusal in human whole blood. Methods Find. Exp. Clin. Pharmacol., 1988, 10(4), 273-277.
[PMID: 3386335]
[5]
Ramis, J.; Mis, R.; Forn, J.; Torrent, J.; Gorina, E.; Jané, F. Pharmacokinetics of triflusal and its main metabolite HTB in healthy subjects following a single oral dose. Eur. J. Drug Metab. Pharmacokinet., 1991, 16(4), 269-273.
[http://dx.doi.org/10.1007/BF03189971] [PMID: 1823870]
[6]
Francia, E.; Marín, A.; García-Rafanell, J. Triflusal: Antithrombotic agent. Drugs Future, 1978, 3, 225-228.
[http://dx.doi.org/10.1358/dof.1978.003.03.199337]
[7]
De la Cruz, J.P.; Pavía, J.; García-Arnés, J.; Sánchez de la Cuesta, F. Effects of triflusal and acetylsalicylic acid on platelet aggregation in whole blood of diabetic patients. Eur. J. Haematol., 1988, 40(3), 232-236.
[http://dx.doi.org/10.1111/j.1600-0609.1988.tb00829.x] [PMID: 2965654]
[8]
De La Cruz, J.P.; Villalobos, M.A.; García, P.J.; Smith-Agreda, J.M.; Sánchez de la Cuesta, F. Effects of triflusal and its main metabolite HTB on platelet interaction with subendothelium in healthy volunteers. Eur. J. Clin. Pharmacol., 1995, 47(6), 497-502.
[http://dx.doi.org/10.1007/BF00193701] [PMID: 7768251]
[9]
de la Cruz, J.P.; Mata, J.M.; Sanchez de la Cuesta, F. Triflusal vs aspirin on the inhibition of human platelet and vascular cyclooxygenase. Gen. Pharmacol., 1992, 23(2), 297-300.
[http://dx.doi.org/10.1016/0306-3623(92)90027-H] [PMID: 1639242]
[10]
Gómez, L.; García Rafanell, J.; Forn, J. Protective effect of triflusal and acetylsalicylic acid against arachidonic acid induced cerebrovascular occlusion in anesthetized rats. Methods Find. Exp. Clin. Pharmacol., 1987, 9(1), 13-17.
[PMID: 3106730]
[11]
Wang, M.; Zhang, Q.; Huang, M.; Zong, S.; Hua, W.; Zhou, W. Pharmacokinetics, safety and tolerability of triflusal and its main active metabolite HTB in healthy Chinese subjects. Drug Res. (Stuttg.), 2014, 64(5), 263-268.
[PMID: 24105106]
[12]
Ge, J.; Ding, L.K.; Yang, J.; Jia, Y.Y.; Lu, C.T.; Ding, Y.; Song, Y.; Song, W.; Wen, A.D. Effect of food on the pharmacokinetics of triflusal and its major active metabolite, 2-hydroxy-4-trifluoromethyl benzoic acid, in healthy subjects. Int. J. Clin. Pharmacol. Ther., 2015, 53(3), 272-276.
[http://dx.doi.org/10.5414/CP202229] [PMID: 25546165]
[13]
Lee, H.W.; Lim, M.S.; Seong, S.J.; Lee, J.; Park, J.; Seo, J.J.; Yun, H.Y.; Baek, I.H.; Kwon, K.I.; Yoon, Y.R. A phase I study to characterize the multiple-dose pharmacokinetics, pharmacodynamics and safety of new enteric-coated triflusal formulations in healthy male volunteers. Expert Opin. Drug Metab. Toxicol., 2011, 7(12), 1471-1479.
[http://dx.doi.org/10.1517/17425255.2011.630661] [PMID: 22098139]
[14]
Cho, H.Y.; Jeong, T.J.; Lee, Y.B. Simultaneous determination of triflusal and its major active metabolite, 2-hydroxy-4-trifluoromethyl benzoic acid, in rat and human plasma by high-performance liquid chromatography. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2003, 798(2), 257-264.
[http://dx.doi.org/10.1016/j.jchromb.2003.09.049] [PMID: 14643505]
[15]
Valle, M.; Barbanoj, M.J.; Donner, A.; Izquierdo, I.; Herranz, U.; Klein, N.; Eichler, H.G.; Müller, M.; Brunner, M. Access of HTB, main metabolite of triflusal, to cerebrospinal fluid in healthy volunteers. Eur. J. Clin. Pharmacol., 2005, 61(2), 103-111.
[http://dx.doi.org/10.1007/s00228-004-0887-0] [PMID: 15711832]
[16]
González-Correa, J.A.; De La Cruz, J.P. Triflusal: an antiplatelet drug with a neuroprotective effect? Cardiovasc. Drug Rev., 2006, 24(1), 11-24.
[http://dx.doi.org/10.1111/j.1527-3466.2006.00011.x] [PMID: 16939630]
[17]
Rosa, M. Antonijoan, Ignasi G, Analia A, Sergio S, Joaquim Balanzó, Iñaki Izquierdo, Javier B, Esther D, Iris Blanch, Manel J Barbanoj.Gastrointestinal safety of triflusal solution in healthy volunteers: a proof of concept endoscopic study. Eur. J. Clin. Pharmacol., 2011, 67, 663-669.
[http://dx.doi.org/10.1007/s00228-011-1004-9]
[18]
Fraj, J.; Valero, A.; Vives, R.; Pérez, I.; Borja, J.; Izquierdo, I.; Picado, C. Safety of triflusal (antiplatelet drug) in patients with aspirin-exacerbated respiratory diseases. Allergy, 2008, 63(1), 112-115.
[http://dx.doi.org/10.1111/j.1398-9995.2007.01473.x] [PMID: 18053020]

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