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1.
PLoS One ; 15(4): e0232263, 2020.
Article in English | MEDLINE | ID: mdl-32348369

ABSTRACT

Gentisic acid (GA), a metabolite of acetylsalicylic acid (ASA), and homogentisic acid (HGA), which is excreted at high levels in alkaptonuria, are divalent phenolic acids with very similar structures. Urine containing HGA is dark brown in color due to its oxidation. We recently reported a new oxidation method of HGA involving the addition of sodium hydroxide (NaOH) with sodium hypochlorite pentahydrate (NaOCl·5H2O), which is a strong oxidant. In the present study, we attempted to oxidize GA, which has a similar structure to HGA, using our method. We herein observed color changes in GA solution and analyzed the absorption spectra of GA after the addition of NaOH with NaOCl·5H2O. We also examined the oxidation reaction of GA using a liquid chromatography time-of-flight mass spectrometer (LC/TOF-MS). The results obtained indicated that GA solution had a unique absorption spectrum with a peak at approximately 500 nm through an oxidation reaction following the addition of NaOH with NaOCl·5H2O. This spectrophotometric method enables GA to be detected in sample solutions without expensive analytical instruments or a complex method.


Subject(s)
Gentisates/chemistry , Spectrophotometry/methods , Alkaptonuria/urine , Aspirin/metabolism , Chromatography, Liquid , Gentisates/metabolism , Gentisates/urine , Homogentisic Acid/chemistry , Humans , Mass Spectrometry , Oxidants , Oxidation-Reduction , Sodium Hydroxide , Sodium Hypochlorite
2.
Talanta ; 143: 328-334, 2015 Oct 01.
Article in English | MEDLINE | ID: mdl-26078167

ABSTRACT

A graphene modified glassy carbon (GR/GCE) sensor has been developed for the determination of aspirin metabolites 2,3- and 2,5-dihydroxybenzoic acids (2,3- and 2,5-DHB). The modified sensor was characterized by Field Emission Scanning Electron Microscopy and Electrochemical Impedance Spectroscopy. The electrochemical behavior of 2,3- and 2,5-DHB was investigated by cyclic and square wave voltammetry. The modified sensor exhibited excellent electrocatalytic activity for the oxidation of 2,3- and 2,5-DHB, leading to a remarkable enhancement in the peak current as compared to the bare sensor. The results were attributed to the enhanced surface area and high conductivity of GR. The anodic peak currents of 2,3- and 2,5-DHB were found to be linear in the concentration range of 1-150 µM and 1-200 µM with the detection limits of 47 nM and 51 nM, respectively. The sensor was capable to determine 2,5-DHB effectively without any interference from the uric acid and other metabolites present in the urine samples. The practical utility of GR/GCE has been successfully demonstrated for the determination of 2,5-DHB in the urine samples of persons undergoing treatment with aspirin.


Subject(s)
Aspirin/pharmacokinetics , Gentisates/urine , Adult , Carbon/chemistry , Dielectric Spectroscopy , Electrodes , Female , Gentisates/analysis , Gentisates/chemistry , Humans , Hydroxybenzoates/analysis , Hydroxybenzoates/chemistry , Limit of Detection , Male , Microscopy, Electron, Scanning , Young Adult
3.
Biopharm Drug Dispos ; 25(1): 1-7, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14716747

ABSTRACT

UNLABELLED: The aim of the present study was to compare the effect produced by juvenile rheumatoid arthritis (JRA) or rheumatic fever (RF) on the pharmacokinetics of acetyl salicylic acid (ASA) and its metabolites in children with autoimmune diseases (AD). METHODS: A prospective, open labelled study was performed in 17 children with JRA and 17 with RF who received a single dose of 25 mg ASA/kg orally. The pharmacokinetics of ASA and its metabolites were determined. The blood and urine levels of each salicylate collected during 24 h were measured by HPLC. A group of 15 healthy teenage volunteers was included as a control group. RESULTS: The maximum plasma concentration, half-life time, area under the curve and the amount of salicylates excreted were statistically different between the JRA and the RF groups, as well as between the RF group and the controls, however, there were no significant differences between the JRA group and the controls. CONCLUSIONS: Dosage schemes must be adjusted for JRA patients, since the half life in these patients is longer than in RF patients. However, due to ample variability of pharmacokinetic parameters it is recommended that dose schemes are individualized on the type of autoimmune disease considered.


Subject(s)
Arthritis, Juvenile/drug therapy , Aspirin/metabolism , Aspirin/pharmacokinetics , Autoimmune Diseases/drug therapy , Rheumatic Fever/drug therapy , Administration, Oral , Adolescent , Area Under Curve , Arthritis, Juvenile/blood , Arthritis, Juvenile/urine , Aspirin/administration & dosage , Autoimmune Diseases/metabolism , Biological Availability , Child , Chromatography, High Pressure Liquid , Female , Gentisates/blood , Gentisates/metabolism , Gentisates/urine , Half-Life , Hippurates/blood , Hippurates/metabolism , Hippurates/urine , Humans , Male , Mexico , Prospective Studies , Rheumatic Fever/blood , Rheumatic Fever/urine , Salicylic Acid/blood , Salicylic Acid/metabolism , Salicylic Acid/urine , Tablets
4.
Eur J Clin Pharmacol ; 57(5): 387-91, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11599656

ABSTRACT

OBJECTIVE: To evaluate the pharmacokinetics of salicin and its major metabolites in humans after oral administration of a chemically standardised willow bark extract. METHODS: Willow bark extract corresponding to 240 mg salicin (1,360 mg, 838 micromol) was ingested by ten healthy volunteers in two equal doses at times 0 h and 3 h. Over a period of 24 h, urine and serum levels of salicylic acid and its metabolites, i.e. gentisic acid and salicyluric acid, were determined using reverse-phase high-performance liquid chromatography. Renal excretion rate, elimination half-life and total bioavailability of salicylates were calculated. RESULTS: Salicylic acid was the major metabolite of salicin detected in the serum (86% of total salicylates), besides salicyluric acid (10%) and gentisic acid (4%). Peak levels were reached within less than 2 h after oral administration. Renal elimination occurred predominantly in the form of salicyluric acid. Peak serum levels of salicylic acid were on average 1.2 mg/l, and the observed area under the serum concentration time curve (AUC) of salicylic acid was equivalent to that expected from an intake of 87 mg acetylsalicylic acid. CONCLUSION: Willow bark extract in the current therapeutic dose leads to much lower serum salicylate levels than observed after analgesic doses of synthetic salicylates. The formation of salicylic acid alone is therefore unlikely to explain analgesic or anti-rheumatic effects of willow bark.


Subject(s)
Benzyl Alcohols/pharmacokinetics , Plants, Medicinal , Administration, Oral , Benzyl Alcohols/administration & dosage , Biological Availability , Gentisates/blood , Gentisates/urine , Glucosides , Half-Life , Hippurates/blood , Hippurates/urine , Humans , Plant Bark/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacokinetics , Reference Standards , Salicylates/blood , Salicylates/urine , Salicylic Acid/blood , Time Factors , Trees
5.
Xenobiotica ; 20(8): 847-54, 1990 Aug.
Article in English | MEDLINE | ID: mdl-2219967

ABSTRACT

1. Metabolism of aspirin was studied in 10 human volunteers who took a therapeutic dose (600 mg) by mouth and in nine patients who took aspirin in overdose. 2. Salicyluric acid was the major urinary metabolite in volunteers (63.1 +/- 8.4% of dose in 0-8 h). In overdose patients, salicyluric acid in urine was decreased (30.0 +/- 8.2%, 0-24 h, P less than 0.001) and there was increased elimination of salicyclic acid (34.1%, P less than 0.005), salicyl acyl glucuronide (14.4%, P less than 0.05) and gentisuric acid (5.3%). 3. Metabolism of orally administered 14C-aspirin in rats over a 10-fold dose range (10-100 mg/kg) resulted in excretion of 81-91% dose in urine in the first 24 h. Salicyclic acid was the major urinary metabolite (43-51% dose). Excretion of salicyluric acid decreased with increasing dose, whereas gentisic acid and salicyl phenolic and acyl glucuronides increased. 4. The profile of aspirin metabolites was qualitatively similar in man and rat but there were quantitative differences. Limited capacity to form salicyluric acid was observed in both species. Dependence on this pathway in rat was low and was compensated by increased utilization of other routes; dependence on salicyluric acid formation in man was high and in overdose, compensation by other routes was incomplete.


Subject(s)
Aspirin/pharmacokinetics , Adolescent , Adult , Animals , Aspirin/administration & dosage , Aspirin/poisoning , Female , Gentisates/urine , Glucuronates/urine , Hippurates/urine , Humans , Kinetics , Male , Middle Aged , Rats , Rats, Inbred Strains , Salicylates/urine , Salicylic Acid
6.
Sangyo Igaku ; 25(5): 399-405, 1983 Sep.
Article in Japanese | MEDLINE | ID: mdl-6668725

ABSTRACT

The effect of the inducers of drug-metabolizing enzymes on the urinary excretion of aspirin metabolites in rats was studied. As to the inducer, rats were administered polychlorinated biphenyls (KC-500: 10, 50, and 100 mg/kg b.w.), phenobarbital (80 mg/kg b.w.), or 3-methylcholanthrene (25 mg/kg) intraperitoneally once a day for three days. The rats were orally administered aspirin (50 mg/kg) on the second-10th day after the pre-treatment with each inducer, and the urine were collected respectively. Aspirin metabolites (salicylic acid, salicyluric acid, and gentisic acid) in the urine were simultaneously determined with high-performance liquid chromatography and the liver microsomal cytochrome P-450 was determined. The results obtained were as follows. Excretion rate of total gentisic acid and salicylate glucuronide in the urine collected for first 6 hours were increased significantly by the pre-treatment with KC-500 or phenobarbital. In the pre-treated rats with various dose of KC-500, positive correlation was observed between the amount of liver microsomal cytochrome P-450 and the urinary excretion rate of gentisic acid (p less than 0.001). Salicylic acid hydroxylating activity of liver microsome was increased in the rats pretreated with KC-500, phenobarbital, or 3-methylcholanthrene. These results show that the increased urinary excretion of total gentisic acid and salicylate glucuronide may be due to the induction of drug-metabolizing enzymes in the liver. Therefore, it may be expected that these two aspirin metabolites are good indicators for the estimation of the activities of drug-metabolizing enzymes in vivo.


Subject(s)
Aspirin/urine , Animals , Biotransformation , Body Weight/drug effects , Cytochrome P-450 Enzyme System/analysis , Gentisates/urine , Male , Methylcholanthrene/pharmacology , Mice , Mice, Inbred Strains , Microsomes, Liver/enzymology , Organ Size/drug effects , Phenobarbital/pharmacology , Rats , Salicylates/urine
9.
Clin Chem ; 26(1): 111-4, 1980 Jan.
Article in English | MEDLINE | ID: mdl-7356541

ABSTRACT

We have developed a specific and sensitive method for the determination of salicylic acid, salicyluric acid, and gentisic acid in urine. Any proteins present are precipitated with methyl cyanide. After centrifugation, an aliquot of the supernate is directly injected into an octadecyl silane reversed-phase chromatographic column, then eluted with a mixture of water, butanol, acetic acid, and sodium sulfate, and quantitated at 313 nm by ultraviolet detection according to peak-height ratios (with internal standard, o-methoxybenzoic acid) or peak heights (no internal standard). The method allows estimates within 25 min. Sensitivity was 0.2 mg/L for gentisic acid, and 0.5 mg/L for both salicyluric and salicylic acid (20-micro L injection volume); response was linear with concentration to at least 2.000 g/L for salicylic acid and metabolites. Analytical recovery of salicylic acid and metabolites from urine is complete. Intra-assay precision (coefficient of variation) is 5.52% at 7.5 mg/L for salicylic acid, 5.01% at 9.33 mg/L for salicyluric acid, and 3.07% at 7.96 mg/L for gentisic acid. Interassay precision is 7.32% at 7.51 mg/L for salicylic acid, 5.52% at 8.58 mg/L for salicyluric acid, and 3.97% at 8.32 mg/L for gentisic acid. We saw no significant interference in urine from patients being treated with various drugs other than aspirin.


Subject(s)
Gentisates/urine , Glycine/analogs & derivatives , Hippurates/urine , Salicylates/urine , Aspirin/metabolism , Chromatography, High Pressure Liquid/methods , Glycine/urine , Humans , Kinetics
14.
Br J Pharmacol ; 37(1): 294-300, 1969 Sep.
Article in English | MEDLINE | ID: mdl-5343352

ABSTRACT

1. A method for the estimation of gentisic acid in urine has been devised which is based on thin-layer chromatography and fluorimetry.2. In man the urinary excretion of gentisic acid accounted for 0.6% of a 0.32 g dose of aspirin and 1.1% of a 1.28 g dose. The increase in the percentage of the dose excreted as gentisic acid provides further evidence that the elimination of salicylic acid cannot be entirely described by first order kinetics.3. Equations are presented which describe the amount of gentisic acid formed from various doses of salicylic acid in a model system, when elimination proceeds partly by simultaneous first order and zero order kinetics. The close agreement of the experimental and theoretical results indicates that the model provides an acceptable interpretation of salicylic acid elimination in man.


Subject(s)
Gentisates/urine , Salicylates/metabolism , Aspirin/metabolism , Chromatography, Thin Layer , Fluorometry , Humans , Kinetics , Methods , Models, Theoretical
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