HPLC Determination of Antipyrine Metabolites

Eichelbaum, Michel; Sonntag, Bärbel; Dengler, H. J.

doi:10.1159/000137550

Cited by 51 publications

(10 citation statements)

References 1 publication

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“…The method reported in this paper utilizes off-line sample preparation, making it possible to automate the whole analysis process. The principal advantage offered by this solid phase extraction procedure is rapidity of analysis, unlike the inconvenience of handling organic solvents and two separate extractions or the use of a normal phase (Eichelbaum et al, 1981) HPLC method.…”

Section: Resultsmentioning

confidence: 99%

“…One of these methods (Tang et al, 1982) uses gas chromatographychemical ionization mass spectrometry (expensive instrumentation found in only a few research laboratories) , others are extremely tedious and cannot measure all the three metabolites simultaneously . Newer methods have been reported for simultaneous determination of A P and its metabolites, but these methods involve time-consuming liquid-liquid extraction (Eichelbaum et al, 1981). We have already established that solid phase extraction of AP offers the advantage of not only superior recovery and reproducibility to liquid-liquid extraction, but also rapidity and convenience (Sarkar and Karnes, 1988).…”

Section: Introductionmentioning

confidence: 99%

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Solid phase extraction and simultaneous high performance liquid chromatographic determination of antipyrine and its major metabolites in urine

Ma¹,

March²,

Ht³

1992

Biomedical Chromatography

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A reversed phase gradient high performance liquid chromatographic method utilizing solid phase extraction has been described for the simultaneous determination of antipyrine (AP), 4-hydroxyantipyrine (COHAP), norantipyrine (NorAP) and 3-hydroxymethylantipyrine (3-OHMAP) in human urine after hydrolysis with pglucuronidase. The C-18 sorbent cartridges were conditioned and urine samples were applied, washed with 1 X 4 mL of phosphate buffer and eluted with 3 X 100 pL of 20% v/v of acetonitrile in methylene chloride. The eluent was evaporated to dryness, reconstituted in 100 pL phosphate buffer and injected. The calibration ranges were 2.0-250 pg/mL (AP), 2.5-250 pg/mL (NorAP), 2.0-250 pg/mL (3-OHMAP) and 5.0-500 pg/mL (4-OHAP) with regression coefficients of 0.998 or greater. Specificity was indicated by the absence of interferences in chromatogram of blank urine from normal as well as cirrhotic patients. The average recovery was 86.7% for AP, 90.5% for NorAP, 85.2% for 4-OHAP and 74.2% for 3-OHMAP. The within-assay precision as indicated by the reproducibility of the assayed spiked urine was less than 9% in all cases and the between-assay precision was less than 12%. The method was applied to studies on antipyrine metabolism in stable cirrhotic patients. Following administration of a single oral dose of about 1000 mg to nine stable cirrhotic patients and eight age-matched healthy volunteers, the cumulative account excreted in the urine up to 48 h for AP and the three metabolites was comparable to other literature reports.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Solid phase extraction and simultaneous high performance liquid chromatographic determination of antipyrine and its major metabolites in urine

Ma¹,

March²,

Ht³

1992

Biomedical Chromatography

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“…The relationship between drug-induced inhibition of AP hepatic metabolism, as in dicated by changes in AP plasma clearance and elimination half-life, to that of other oxi dized drugs is highly variable [24], AP biotransformation by 3 separate cytochrome P-450-dependent reactions -2-hydroxylations and N-demethylation [25] -permits more sensitive assessment by evaluating forma tion of each metabolite since the rates of these enzymatic reactions may not directly relate to pharmacokinetic parameters of the parent drug. Rates of individual metabolite formation mav therefore better reflect activ ity of specific subsets of cytochrome P-450 isoenzymes [26].…”

Section: Discussionmentioning

confidence: 99%

Effects of Nifedipine on Hepatic Drug Oxidation

1988

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To determine whether inhibition of drug oxidation is a general property of all calcium antagonist drugs or just of a few, we measured effects of therapeutic doses of nifedipine on antipyrine biotransformation. Antipyrine was administered in random order to 10 subjects while drug-free and while taking nifedipine 30 mg 3 times daily. Total antipyrine clearance (means ± SE, 43.1 ± 4.8 control vs. 50.4 ± 6.5 ml/min; NS) tended to increase but not significantly. Elimination half-life decreased slightly (13.7 ± 1.0 control vs. 11.7 ± 0.9; p < 0.05). Antipyrine metabolite excretion, measured to evaluate selective oxidative pathways, was unaffected by concurrent nifedipine administration. Nifedipine in therapeutic doses had no effect on antipyrine oxidation, unlike verapamil and diltiazem, both of which inhibit hepatic drug oxidation. Inhibition of drug oxidation appears not to be a general property of calcium antagonist drugs.

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“…The detection limit of metoprolol in plasma and urine was 20 ~g/l for this method; the level of precision was 6.53% to 4.70% (intersubject variation; X +__ SD). The antipyrine concentration in plasma was determined by the method described by Eichelbaum et al [13], with minor modifications. Antipyrine was extracted from plasma samples of 0.5 ml by solid-phase extraction (Baker 7020-1 disposable columns) with phenacetin as internal standard.…”

Section: Methodsmentioning

confidence: 99%

Influence of nitrendipine and verapamil on plasma levels, urinary excretion, and beta-blocking effect of metoprolol

Kirch

Santos

Geller

et al. 1988

Cardiovasc Drug Ther

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Following randomized allocation eight healthy volunteers were treated for 1 week each with metoprolol alone (100 mg twice daily), verapamil 80 mg three times a day plus metoprolol 100 mg twice daily, and with nitrendipine 20 mg twice daily. Plasma levels and urinary recovery of the beta-blocker, antipyrine clearance, and heart rate on exercise were measured. Verapamil and nitrendipine slightly prolonged elimination half-life of metoprolol. The urinary recovery of the parent beta-blocker and of its alpha-hydroxy metabolite was elevated by both calcium antagonists (verapamil and nitrendipine). Exercise tachycardia (150 beats/min without drugs) was inhibited more pronounced on the combination therapies than under metoprolol administration alone. Results of the present study indicate that calcium antagonists enhance inhibition of exercise tachycardia caused by metoprolol, possibly due to their binding to myocardial beta-adrenergic receptors which is known from the literature. As both calcium antagonists did not increase plasma levels of metoprolol, in the present study a kinetic interaction between the beta-blocker and the calcium channel blockers investigated does not appear to be responsible for the pharmacodynamic effects observed.

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HPLC Determination of Antipyrine Metabolites

Cited by 51 publications

References 1 publication

Solid phase extraction and simultaneous high performance liquid chromatographic determination of antipyrine and its major metabolites in urine

Solid phase extraction and simultaneous high performance liquid chromatographic determination of antipyrine and its major metabolites in urine

Effects of Nifedipine on Hepatic Drug Oxidation

Influence of nitrendipine and verapamil on plasma levels, urinary excretion, and beta-blocking effect of metoprolol

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