Metabolites, plasma urine

Lau, G.S.N. Critchley, J.A.J.H. The estimation of paracetamol and its major metabolites in both plasma and urine by a single high-performance liquid chromatography assay. J.Pharm.Biomed.Anal., 1994, 12, 1563-1572 [extracted metabolites plasma urine blood LOD 1 ng]... 

Methandrostenolone and its metabolites equine plasma/urine liq-liq extraction phenyl C18 C8 UV and MS-MS 30... 

MAO converts dopamine to DOPAC (3,4-dihydrox-yphenylacetic acid), which can be further metabolized by COMT to form homovanillic acid (HVA). HVA is the main product of dopamine metabolism and the principal dopamine metabolite in urine. Increased neuronal dopaminergic activity is associated with increases in plasma concentrations of DOPAC and HVA. COMT preferentially methylates dopamine at the 3 -hydroxyl position and utilizes S-adenosyl-L-methio-nine as a methyl group donor. COMT is expressed widely in the periphery and in glial cells. In PD, COMT has been targeted since it can convert l-DOPA to inactive 3-OMD (3-O-methyl-dopa). In the presence of an AADC inhibitor such as carbidopa, 3-OMD is the major metabolite of l-DOPA treatment. 

Alkaloids, e.g. laubasine and its metabolites in plasma, urine and bile... 

Most of the tests that were developed for detection of cannabinoids in plants have shown that antibodies are specific for the cannabinoid structure. Because of this specifity these tests can be extensively applied for the detection of cannabinoids and metabolites in human body fluids such as plasma, urine, and oral fluids. Many different kits based on these methods were developed and they are commercially available, for example Oratect, Branan or Uplink, and OraSure. We must consider, however, that no humans have the same metabolite profile in their blood and that cross-reactivity may always occur [122,123]. Nevertheless, these tests offer a simple way of excluding most of the suspicious samples, but the results still have to be confirmed with a second method such as GC-MS [124,125]. 

Applicators, mixers, loaders, and others who mix, spray, or apply pesticides to crops face potential dermal and/or inhalation exposure when handling bulk quantities of the formulated active ingredients. Although the exposure periods are short and occur only a few times annually, an estimate of this exposure can be obtained by quantifying the excreted polar urinary metabolites. Atrazine is the most studied triazine for potential human exposure purposes, and, therefore, most of the reported methods address the determination of atrazine or atrazine and its metabolites in urine. To a lesser extent, methods are also reported for the analysis of atrazine in blood plasma and serum. 

Exposure. No biomarkers of exposure were identified that were specific to diisopropyl methylphosphonate. Although standard procedures exist for identifying diisopropyl methylphosphonate s primary metabolite (IMP A) in plasma, urine, and feces (Weiss et al. 1994), the detection of IMP A is not unique to diisopropyl methylphosphonate exposure. IMPA is also a major metabolite of GB (Sarin) (Little et al. 1986). In addition, IMPA is cleared from the body rapidly, making it a useful indicator for recent exposure only. 

In a bioanalytical method, analyses of blank samples (plasma, urine, or other matrix) should be obtained from at least six sources. Each blank sample should be tested for the possible interference of endogenous substances, metabolites, or degradation products. The response of the peaks interfering at the retention time of the analyte should be less than 20% of the response of a lower quantitation limit standard, and should be less than 5% of the response of the internal standard that was used [18, 19]. For dissolution studies, the dissolution media or excipients should not give a peak or spot that has an identical Rt or Rf value with the analyte [20]. 

The LC-MS/MS technique has been used to quantify and identify phenolic compounds. In order to quantify, multiple reaction monitoring (MRM), in which there is a combination of the precursor ion and one of its daughter fragments, is used to characterize a particular compound. This behavior should be as specific as possible in samples with a complex mixture of phenolic compounds. This technique has been largely used to quantify phenolic compound metabolites in urine and plasma (Urpf-Sarda and others 2005, 2007). In this context, LC-ESI-MS/MS with negative mode has been applied for the identification of a variety of phenolic compounds in a cocoa sample (Sanchez-Rabaneda and others 2003 Andres-Lacucva and others 2000). 

Mutations in the gene for adenylosuccinate lyase (ASL), inherited as an autosomal recessive disorder in purine metabolism, are associated with severe mental retardation and autistic behavior, but apparently not self-mutilation [10, 11]. This enzyme catalyzes two distinct reactions in the de novo biosynthesis of purines the cleavages of adenylosuccinate (S-Ado) and succinylaminoimidazole carboxamide ribotide (SAICAR), both of which accumulate in plasma, urine and cerebrospinal fluid of affected individuals [12]. Measurements of these metabolites in urine... 

When 20 mg/kg of methimazole was administered i.p. or orally to rats, urinary methimazole glucuronides accounted for 36-48% of the dose in 24 hours. The only other urinary metabolite accounted for 10-20% and was not characterized. An additional 14-20% of methimazole was excreted unchanged in 24 hour urine. The bile contained methimazole glucuronide and two unidentified metabolites. One of which was the same as the unidentified urinary metabolites. Plasma proteins bound 5% of methimazole which had no affinity for any specific tissue. Methimazole had a much greater CHCI3/H2O partition coefficient and 1 0 solubility than did propylthiouracil. Between 77 and 95% of the methimazole was excreted in the urine and approximately 10% in the bile. Since fecal excretion was neglegible an enter-ohepatic circulation was present. The half life of urinary excretion was 5-7 hours regardless of the route of administration (15). 

Levels of cyanide and its metabolite thiocyanate in blood serum and plasma, urine, and saliva have been used as indicators of cyanide exposure in humans, particularly in workers at risk of occupational exposures, in smokers or nonsmokers exposed to sidestream or environmental tobacco smoke, in populations exposed to high dietary levels of cyanide, and in other populations with potentially high exposures (see Section 5.6). The correlation between increased cyanide exposure and urinary thiocyanate levels was demonstrated in workers exposed to 6.4-10.3 ppm cyanide in air (El Ghawabi et al. 1975). In another study, blood cyanide concentrations were found to vary from 0.54 to 28.4 pg/100 mL in workers exposed to approximately 0.2-0.8 ppm cyanide in air, and from 0.0 to 14.0 pg/100 mL in control workers... 

The biological applications of NMR include the study of the structure of macromolecules such as proteins and nucleic acids and the study of membranes, and enzymic reactions. Newer methods and instruments have overcome, to a large extent, the technical difficulties encountered with aqueous samples and the analysis of body fluids is possible, permitting the determination of both the content and concentration of many metabolites in urine and plasma. NMR is not a very sensitive technique and it is often necessary to concentrate the sample either by freeze drying and dissolving in a smaller volume cm- by solid phase extraction methods. 

The use of HPLC to analyze biogenic amines and their acid metabolites is well documented. HPLC assays for classical biogenic amines such as norepinephrine (NE), epinephrine (E), dopamine (DA), and 5-hydroxytryptamine (5-HT, serotonin) and their acid metabolites are based on several physicochemical properties that include a catechol moiety (aryl 1,2-dihydroxy), basicity, easily oxidized nature, and/or native fluorescence characteristics (Anderson, 1985). Based on these characteristics, various types of detector systems can be employed to assay low concentrations of these analytes in various matrices such as plasma, urine, cerebrospinal fluid (CSE), tissue, and dialysate. 

Frederiksen H, Jorgensen N, Andersson AM (2010) Correlations between phthalate metabolites in urine, serum, and seminal plasma from young Danish men determined by isotope dilution liquid chromatography tandem mass spectrometry. J Anal Toxicol 34 400-410... 

In the horse, hydroxylation is more important than acetylation as a metabolic pathway, with hydroxylation at the 5 position being dominant over hydroxylation of the 6-methyl group. Low percentages of metabolites are present in plasma, for N -SDM, 0.6 to 0.9 % for SCH2OH, 0.38 to 0.71 % and for SOH, 0.38 to 6.7 %. The plasma concentration-time curves of the metabolites run parallel to that of SDM. The elimination half-life of sulfadimidine varies between 5 and 14 h. The main metabolite in urine, accounting for 50 % of the drugs present (Table III), is the SOH and its glucuronide. 

The primary endpoint of the toxicokinetic studies is the concentration-time prohle of the substance in plasma/blood and other biological fluids as well as in tissues. The excretion rate over time and the amount of metabolites in urine and bile are further possible primary endpoints of kinetic studies, sometimes providing information on the mass balance of the compound. From the primary data, clearance and half-life can be derived by several methods. From the excretion rate over time and from cumulative urinary excretion data and plasma/blood concentration measured during the sampling period, renal clearance can be calculated. The same is the case for the bUiary excretion. 

Metabolism - No metabolites have been detected in plasma, urine, or feces, indicating a lack of either systemic or presystemic metabolism. 

Metabolism/Excretion-The drug undergoes extensive hepatic metabolism to inactive metabolites. Plasma elimination is biphasic half-life is 2 hours during the first 10 hours, and 8 hours thereafter. The major excretory route is enterohepatic. From 85% to 90% is excreted in bile and feces and 13% in urine. 

The analysis of many drugs and metabolites in urine samples has been reported also as the analysis of these substances in serum or plasma samples. Therefore, such works are cited in Section VIII,B,1 and will not be repeated here. Urinary components can be useful indicators of one s metabolic state and therefore their analysis is frequently helpful in estab-... 

The levels of fluoride in body fluids (plasma, saliva, urine) give some indication of recent fluoride intake. Fluoride ion does not produce any metabolites, and so is itself the measured indicator. This indicator, however, does not well reflect the fluoride body burden or the accumulation of fluoride in the body, because the relation between fluoride concentrations in bone and in extracellular fluids is incompletely defined. The concentration of fluoride in plasma, urine, saliva and dental plaque is dependent on the intake via water, diet, fluoride supplements and fluoride-containing dentifrices [92-97],... 

Pharmacokinetics Peak response occurs in 4-8 wk. The duration of a single dose is about 10 hr. Hydrolyzed to unoprostone free acid form in the cornea. Rapidly eliminated from plasma. Excreted as metabolites in urine. Half-life 14 min. 

Heggie GD, Sommadossi IP, Cross DS et al. Clinical pharmacokinetics of 5-fluorouracil and its metabolites in plasma, urine, and bile. Cancer Res 1987 47 2203-2206. 

For isohexide nitrates gas-liquid chromatographic separation methods using OF-1 (Ref. 52), OV-101 (Refs. 53-59), OV-17 (Ref 60), or OV-210 (Ref 61) columns have been reported. Most of the methods described are used to detect traces of nitrates, as well as of their metabolites, in urine and plasma probes.62-69 All known isohexide nitrates can be measured in mixtures by using a DB-5 capillary column.70-71 Electron-capture detection was applied for the g.l.c. determination of isosorbide dinitrate71 and its metabo-lites.7,b... 

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