Acetaminophen in the guinea pig: metabolite identification in blood, urine, and bile

1986 ◽  
Vol 64 (1) ◽  
pp. 72-76 ◽  
Author(s):  
S. Hidvegi ◽  
D. J. Ecobichon
Keyword(s):  
High Performance Liquid Chromatography ◽  
High Performance ◽  
High Capacity ◽  
Parent Drug ◽  
Metabolite Identification ◽  
Oral Doses ◽  
Plasma Half Life ◽  
Sulphate Conjugate ◽  
Bile Samples ◽  
Predominant Product

The biotransformation of single acute oral doses of acetaminophen (100 mg/kg body weight) in adult male guinea pigs was studied by collecting serial blood, urine, and bile samples post-treatment and identifying and quantitating the concentrations of parent drug and excretory products by high performance liquid chromatography. The plasma half-life (βt/2) (mean ± SD) of acetaminophen was 1.87 ± 0.30 h, while that of the only metabolite detected in plasma, the glucuronide, was 2.41 ± 0.64 h. In 24-h urine samples, the predominant product was the glucuronide (90%) with a small amount of the sulphate conjugate (7.0%) and approximately 3.0% acetaminophen. In bile, the glucuronide was the major metabolite detected initially but, with time, this product decreased concomitantly with an increase in the cysteinyl conjugate. No sulphate was detected in bile but two unidentified metabolites were detected, having distinct column retention times and comprising approximately 6–10% of the total excretory products. The results demonstrated that glucuronidation is a high capacity biotransformation pathway for acetaminophen in this species, only small amounts of other conjugated products being detectable under usual circumstances.

Denaturing High Performance Liquid Chromatography and Bioinformatics - Two Modern Tools for Extracellular Superoxide Dismutase (SOD3) Gene Promoter Analysis

2008 ◽  
Vol 59 (7) ◽  
Author(s):  
Corina Samoila ◽  
Alfa Xenia Lupea ◽  
Andrei Anghel ◽  
Marilena Motoc ◽  
Gabriela Otiman ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Transcription Factors ◽  
Liquid Chromatography ◽  
Dna Sequences ◽  
High Performance ◽  
Zinc Finger Protein ◽  
High Capacity ◽  
Gene Promoter ◽  
Experimental Approaches ◽  
Myeloid Zinc Finger

Denaturing High Performance Liquid Chromatography (DHPLC) is a relatively new method used for screening DNA sequences, characterized by high capacity to detect mutations/polymorphisms. This study is focused on the Transgenomic WAVETM DNA Fragment Analysis (based on DHPLC separation method) of a 485 bp fragment from human EC-SOD gene promoter in order to detect single nucleotide polymorphism (SNPs) associated with atherosclerosis and risk factors of cardiovascular disease. The fragment of interest was amplified by PCR reaction and analyzed by DHPLC in 100 healthy subjects and 70 patients characterized by atheroma. No different melting profiles were detected for the analyzed DNA samples. A combination of computational methods was used to predict putative transcription factors in the fragment of interest. Several putative transcription factors binding sites from the Ets-1 oncogene family: ETS member Elk-1, polyomavirus enhancer activator-3 (PEA3), protein C-Ets-1 (Ets-1), GABP: GA binding protein (GABP), Spi-1 and Spi-B/PU.1 related transcription factors, from the Krueppel-like family: Gut-enriched Krueppel-like factor (GKLF), Erythroid Krueppel-like factor (EKLF), Basic Krueppel-like factor (BKLF), GC box and myeloid zinc finger protein MZF-1 were identified in the evolutionary conserved regions. The bioinformatics results need to be investigated further in others studies by experimental approaches.

Specific 3H radioimmunoassay with a monoclonal antibody for monitoring cyclosporine in blood.

1988 ◽  
Vol 34 (2) ◽  
pp. 257-260 ◽  
Author(s):  
P E Ball ◽  
H Munzer ◽  
H P Keller ◽  
E Abisch ◽  
J Rosenthaler
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
High Performance Liquid Chromatography ◽  
High Performance ◽  
Limit Of Detection ◽  
Parent Drug ◽  
Sample Volume ◽  
Specific Radioimmunoassay ◽  
The Mean ◽  
Blood Specimens

Abstract A specific radioimmunoassay involving a mouse monoclonal antibody to cyclosporine has been developed for monitoring the parent drug in blood. Pretreatment with methanol removes cyclosporine from the erythrocytes. The limit of detection is about 12 micrograms/L, sample volume is 50 microL of blood, and within- and between-assay CVs are less than 7%. Assay results correlated well with those obtained by "high-performance" liquid chromatography (HPLC) for liver (n = 42), for heart (n = 64), for bone-marrow (n = 36), and for kidney (n = 140). For blood specimens obtained from patients treated with cyclosporine postoperatively for as long as 65 months, the mean RIA/HPLC ratio in all with transplant indications was close to 1. Therefore, the specific radioimmunoassay apparently can be used instead of HPLC to measure the parent drug in blood.

scholarly journals Pharmacokinetic profile and metabolite identification of bornyl caffeate and caffeic acid in rats by high performance liquid chromatography coupled with mass spectrometry

RSC Advances ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 4015-4027 ◽  
Author(s):  
Baimei Shi ◽  
Lingjian Yang ◽  
Tian Gao ◽  
Cuicui Ma ◽  
Qiannan Li ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Single Dose ◽  
Metabolic Profile ◽  
High Performance ◽  
Ion Trap ◽  
Metabolite Identification ◽  
Pharmacokinetic Profile ◽  
Tof Ms

We revealed the metabolic profile of bornyl caffeate by HPLC-Q-TOF/MS, and then simultaneously examined the pharmacokinetics of bornyl caffeate and CA after administration of a single dose of bornyl caffeate by HPLC ion trap MS.

scholarly journals High-Capacity Screening of Arylalkylamine N-Acetyltransferase Inhibitors using a High-Performance Liquid Chromatography System

2000 ◽  
Vol 5 (5) ◽  
pp. 361-368 ◽  
Author(s):  
Gilles Ferry ◽  
Jean A. Boutin
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
High Performance ◽  
Enzyme Inhibitor ◽  
False Negative ◽  
High Capacity ◽  
Screening Methods ◽  
Enzymatic System ◽  
Systematic Screening ◽  
Hplc System

Systematic screening is a natural development of any pharmacological program. Most enzyme inhibitor screens use indirect or "aspecific" methods, such as colorimetric or fluorimetric ones. These screening methods cause quite a few false-positive and false-negative hits. In order to limit these as much as possible, we developed a methodology using a high-performance liquid chromatography (HPLC) system for the medium throughput screening of serotonin N-acetyltransferase inhibitors. The core of this screening system is (1) the dramatic shortening of the analytical time down to 100 s per run by using a high-performance analytical column (Turbo), and (2) the use of absorption as opposed to radioactivity for detection of the product of the reaction (N-acetylserotonin). This system permits the analysis of about 1,000 compounds per day to be performed with a single HPLC system. This enzymatic system was taken as an example, because the methodology can be extended to many other enzymes, particularly transferases, phosphatases, and kinases.

scholarly journals Glycated Haemoglobin: An Assessment of High Capacity Liquid Chromatographic and Immunoassay Methods

1992 ◽  
Vol 29 (5) ◽  
pp. 494-505 ◽  
Author(s):  
Susan J Standing ◽  
Richard P Taylor
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
High Throughput ◽  
High Performance ◽  
High Capacity ◽  
Glycated Haemoglobin ◽  
Coefficients Of Variation ◽  
Operation Flexibility ◽  
Liquid Chromatographic

We have assessed five high-throughput systems for the measurement of glycated haemoglobin and have reviewed published evaluations of individual analysers. All systems offered better precision than a widely used electroendosmosis method. The low pressure chromatography and immunoassay systems demonstrated greater between-batch imprecision than the high performance liquid chromatography analysers, the latter achieving the proposed analytical goal of between-batch coefficients of variation less than 5%. Agreement between all systems measuring HbA1 was good but there was variability amongst observed HbA1c values. The systems were also assessed for their quality of chromatographic separation, simplicity of operation, flexibility, cost and potential for interference by other haemoglobins.

scholarly journals Rifampin Reduces Concentrations of Trimethoprim and Sulfamethoxazole in Serum in Human Immunodeficiency Virus-Infected Patients

2001 ◽  
Vol 45 (11) ◽  
pp. 3238-3241 ◽  
Author(s):  
Esteban Ribera ◽  
Leonor Pou ◽  
Antoni Fernandez-Sola ◽  
Francisco Campos ◽  
Rosa M. Lopez ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
High Performance Liquid Chromatography ◽  
High Performance ◽  
Parent Drug ◽  
Time Curve ◽  
Once Daily ◽  
Concentration Time ◽  
Antituberculosis Treatment ◽  
Immunodeficiency Virus ◽  
Before And After

ABSTRACT To determine whether rifampin reduces concentrations of trimethoprim (TMP) and sulfamethoxazole (SMX) in serum of human immunodeficiency virus (HIV)-infected persons, levels of these agents were determined by high-performance liquid chromatography before and after more than 12 days of standard antituberculosis treatment for 10 patients who had been taking one double-strength tablet of co-trimoxazole once daily for more than 1 month. Statistically significant, 47 and 23% decreases in TMP and SMX mean areas under the concentration-time curve from 0 to 24 h (AUC0–24), respectively, were observed after administration of rifampin.N-Acetyl-SMX profiles without and with rifampin were similar. The steady-state AUC0–24 metabolite/parent drug ratio increased by 32% with rifampin administration. Our study shows that rifampin reduces profiles of TMP and SMX in serum of HIV-infected patients.

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