High-performance liquid chromatography of sulfapyridine and its acetyl and glucuronide metabolites in rat and human urine

Pharmaceutisch Weekblad Scientific Edition

Kolmer

1992

Probenecid with its phase-I metabolites, and phase-II glucuronide conjugate can be analysed by a gradient high pressure liquid chromatographic method. Probenecid glucuronide in plasma with pH 7.4 is not stable and declines to 10% of the original value within 6 h (t1/2 approximately 1 h). Probenecid glucuronide is stable in urine with pH 5.0, moderately unstable at pH 6.0 (t1/2 approximately 10 h), and unstable at pH 8.0 (t1/2 approximately 0.5 h). Probenecid glucuronide is stable in water and 0.01 mol/l phosphoric acid in the autosampler of the high pressure liquid chromatograph. The decrease in concentration in water is 5.5% during 9 h and 0% in diluted acid. Probenecid glucuronide and the phase-I metabolites were not detectable in plasma. The main compound in fresh urine is the phase-II conjugate probenecid glucuronide (62% of a 500 mg dose); the phase-I metabolites are present and only a trace of probenecid is present. The percentage of the dose of the phase-I metabolites varies between 5 and 10, while hardly any probenecid is excreted unchanged (0.33%).

Section: Discussionsupporting

confidence: 85%

Direct measurement of probenecid and its glucuronide conjugate by means of high pressure liquid chromatography in plasma and urine of humans

Pharmaceutisch Weekblad Scientific Edition

Kolmer

1992

“…In this respect, system A (parent drug + glucuronide) is comparable to those described earlier [6][7][8][9][10][11]. With system A the plasma concentration of parent drug and glucuronide metabolite can be measured.…”

Section: Discussionmentioning

confidence: 94%

“…Recently, we contributed to the development of the direct high pressure liquid chromatographic (HPLC) analysis of drug-glucuronide conjugates, exemplified in the N-glucuronides of sulfadimethoxine [6 7], sulfa-6-monomethoxine [8], sulfaphenazole [9], the O-glucuronide of parahydroxyphenytoin [10], and of 5-hydroxysulfapyridine [11]. These glucuronide conjugates were achiral compounds.…”

Section: Introductionmentioning

confidence: 99%

Direct high pressure liquid chromatographic analysis and preliminary pharmacokinetics of enantiomers of oxazepam and temazepam with their corresponding glucuronide conjugates

Pharmaceutisch Weekblad Scientific Edition

Baars²,

Wuis³

1991

Three high pressure liquid chromatographic systems for the separation of oxazepam, temazepam and their glucuronides (system A), the separation of their R,S glucuronide diastereomers (system B) and the chiral separation of the parent drugs (system C) are described. Preliminary pharmacokinetics of R,S-oxazepam and R,S-temazepam in a human volunteer reveal that the protein binding of the glucuronides is lower than that of the parent drugs, but that there is no difference in protein binding between the R-oxazepam/temazepam and S-oxazepam/temazepam and their corresponding glucuronides. The S-glucuronide is the main metabolite formed and excreted by man. The plasma ratio R/S-glucuronide is 1:1 for both oxazepam and temazepam. The renal clearance of R-temazepam, and S-temazepam are similar, and those of R-oxazepam and S-oxazepam tend to be different.

“…N4-acetylsulphapyridine (N4), 5-hydroxysulphapyridine (SOH), and N4-acety1-5-hydroxysulphapyridine (N4OH) were synthesised and isolated as described elsewhere (4,15,24). Sulphadiazine (S) was obtained from OPG (Utrecht, The Netherlands).…”

Section: Drugsmentioning

confidence: 99%

“…Glucuronide conjugates are in general measured after treatment of the biological matrix with Pglucuronidase. Recently we reported the direct HPLC measurement with gradient HPLC and UV detection of the 0-glucuronides of sulphapyridine in the urine of man and rat (20,24 N Reptiles, such as the freshwater turtle Pseudemys scripta elegans, possess metabolic pathways which are in principle similar to those of mammals, but the orchestration is different. For instance, in the group of sulphonamides, sulphadimethoxine is mainly 0-dealkylated by the turtle, glucuronidated at the NI-position by man, and acetylated at the N4-position by pigs (15,20,21,22).The high performance liquid chromatography (HPLC) chromatograms of samples of the cumulated excrements of water turtles contain no interfering endogenous compounds and appear 'clean', like reference samples.…”

Section: Introductionmentioning

confidence: 99%

Novel oxidative pathways of sulphapyridine and sulphadiazine by the turtlePseudemys scripta elegans

Vree²,

Kolmer

1991

Veterinary Quarterly

Self Cite

SUMMARY.The sulphonamides sulphapyridine and sulphadiazine show novel hydroxy metabolites in the turtle Pseudemys scripta elegans. In the excreta of the turtles the monohydroxy metabolites 4-hydroxy-and 5-hydroxysulphapyridine and the dihydroxy metabolite 4,5-dihydroxysulphapyridine were detected.Of sulphadiazine only dihydroxy metabolites 4,5-and 4,6-dihydroxysulphadiazine were detected. About 70-90% of the dose of sulphapyridine was recovered, while this figure varied between 48 and 69% for sulphadiazine.