Isolation, identification and determination of sulfamethoxazole and its known metabolites in human plasma and urine by high-performance liquid chromatography

作者: T.B. Vree , A.J.A.M. van der Ven , C.P.W.G.M. Verwey-van Wissen , E.W.J. van Ewijk-Beneken Kolmer , A.E.M. Swolfs

DOI: 10.1016/0378-4347(94)00232-0

关键词: Quantitative analysis (chemistry)Antibacterial agentMetaboliteHigh-performance liquid chromatographyMass spectrometryUrineChemistryChromatographyPharmacokineticsReversed-phase chromatography

摘要: From human urine the following metabolites of sulfamethoxazole (S) were isolated by preparative HPLC: 5-methylhydroxysulfamethoxazole (SOH), N4-acetyl-5-methylhydroxysulfamethoxazole (N4SOH) and sulfamethoxazole-N1-glucuronide (Sgluc). The compounds identified NMR, mass spectrometry, infrared hydrolysis β-glucuronidase ratio capacity factors. analysis S N4-acetylsulfamethoxazole (N4), SOH, N4-hydroxysulfamethoxazole (N4OH), N4SOH, Sgluc in plasma samples was performed with reversed-phase gradient HPLC UV detection. In plasma, N4 could be detected high concentrations, while other present only minute concentrations. urine, conjugates present. quantitation limit are respectively: 0.10 μg/ml; N4SOH 0.13 N4OH 0.18 SOH 0.20 0.39 μg/ml. limits are: 1.4 1.5 1.9 3.5 4.1 method applied to studies healthy subjects HIV positive patients.

参考文章(20)
A. Calvin Bratton, E.K. Marshall, A NEW COUPLING COMPONENT FOR SULFANILAMIDE DETERMINATION Journal of Biological Chemistry. ,vol. 128, pp. 537- 550 ,(1939) , 10.1016/S0021-9258(18)73708-3
A.J.AM. van der Ven, P.P. Koopmans, J.W.M. van der Meer, T.B. Vree, Adverse reactions to co-trimoxazole in HIV infection The Lancet. ,vol. 338, pp. 431- 433 ,(1991) , 10.1016/0140-6736(91)91046-W
Theodore C. Kram, Separation of Sulfa Drugs by High Speed Liquid Chromatography Journal of Pharmaceutical Sciences. ,vol. 61, pp. 254- 256 ,(1972) , 10.1002/JPS.2600610225
Johannes H. Proost, Dirk K.F. Meijer, MW/Pharm, an integrated software package for drug dosage regimen calculation and therapeutic drug monitoring Computers in Biology and Medicine. ,vol. 22, pp. 155- 163 ,(1992) , 10.1016/0010-4825(92)90011-B
T.B. Vree, E.W.J.Beneken Kolmer, M. Martea, R. Bosch, M. Shimoda, High-performance liquid chromatography of sulphadimethoxine and its N1-glucuronide, N4-acetyl and N4-acetyl-N1-glucuronide metabolites in human plasma and urine Journal of Chromatography B: Biomedical Sciences and Applications. ,vol. 526, pp. 119- 128 ,(1990) , 10.1016/S0378-4347(00)82489-5
T.B. Vree, Y.A. Hekster, A.M. Baars, J.E. Damsma, E. Van Der Kleijn, Determination of trimethoprim and sulfamethoxazole (co-trimoxazole) in body fluids of man by means of high-performance liquid chromatography Journal of Chromatography B: Biomedical Sciences and Applications. ,vol. 146, pp. 103- 112 ,(1978) , 10.1016/S0378-4347(00)81294-3
T. B. Vree, E. W. J. Beneken Kolmer, Y. A. Hekster, High pressure liquid chromatographic analysis and preliminary pharmacokinetics of sulfaphenazole and its N2-glucuronide and N4-acetyl metabolites in plasma and urine of man Pharmaceutisch Weekblad Scientific Edition. ,vol. 12, pp. 243- 246 ,(1990) , 10.1007/BF01967825
T. B. Vree, E. W. J. Beneken Kolmer, Y. A. Hekster, Pharmacokinetics, N1-glucuronidation and N4-acetylation of sulfamethomidine in humans Pharmacy World & Science. ,vol. 12, pp. 198- 206 ,(1990) , 10.1007/BF01988875
T. B. Vree, M. W. Tijhuis, J. F. M. Nouws, Y. A. Hekster, Isolation and identification of 4-hydroxysulfamerazine and preliminary studies on its pharmacokinetics in dogs. Pharmacy World & Science. ,vol. 6, pp. 80- 87 ,(1984) , 10.1007/BF01953959