Mass Fragmentographic Method Research Articles

Mass fragmentographic assay for 25‐hydroxyvitamin D in plasma without derivatization: Enhanced sensitivity for metabolites of vitamins D2 and D3 after pre‐column dehydration

AbstractA mass fragmentographic method for the measurement in plasma of underivatized, dehydrated 25‐hydroxyvitamin D2 and 25‐hydroxyvitamin D3 was developed. Quantitative dehydration of vitamin D metabolites was achieved prior to gas chromatography using a new high‐temperature injection system and a small precolumn packed with aluminium powder in the injection port, followed by mass fragmentography on an inexpensive bench‐top mass spectrometer. Plasma (2 ml) was incubated with hexadeuteriated 25‐hydroxyvitamin D3 prior to acetonitrile extraction and purification using cartridges pre‐packed with microparticulate silica using reversed‐ and normal‐phase solvent systems. After purification, capillary gas chromatography mass spectrometry was carried out following dehydration of the secosteroids on the aluminium power pre‐column at 400°C. High‐intensity dehydrated molecular ions were produced which were used for selected ion monitoring. The assay sensitivity for 25‐hydroxyvitamin D was approximately 1 ng ml−1. The intra‐assay variation was less than 7% and the recovery of added standard was quantitative. It is suggested that this method may be used to provide target values for much needed quality control schemes to monitor assays routinely used in the estimation of 25‐hydroxyvitamin D. The behaviour of a number of other hydroxylated vitamin D metabolites, when injected without derivatization on to a gas chromatographic column, was also investigated.

Plasma concentrations of lignocaine after rectal administration

Summary The rectal administration of the premedication for children is often preferred in order to minimise discomfort. The appropriate dose of atropine when rectally administered is poorly documented. In this study six children weighing between 7.5 and 41 kg were given 0.02 mg atropine sulphate/kg rectally and four children were given the same doses intramuscularly. Plasma concentrations of atropine were analysed at several intervals after administration by a modified mass fragmentographic method accurate to 0.1 ng/ml. Peak plasma concentration of atropine, reached after 15 minutes, was 0.7 ng/ml, compared with 2.40 ng/ml reached after 5 minutes for the intramuscular route. The relation between intramuscular and rectal peak concentration was 3.2:1.

Quantification of dimethindene in plasma by gas chromatography—mass fragmentography using ammonia chemical ionization

A gas chromatographic—mass fragmentographic method using ammonia chemical ionization for the determination of dimethindene in human plasma is described. The drug was isolated from plasma by liquid—liquid extraction with hexane—2-methylbutanol. Plasma components were separated on a capillary column coated with chemically bonded methyl silicone. For detection of dimethindene, its quasi-molecular ion (M + H +) was mass fragmentographically monitored after chemical ionization with ammonia as reagent gas. Dimethindene was quantified using methaqualone as the internal standard: the quantification limit in plasma was 0.2 ng/ml, the within-run precision was 8.0% and the inter-run precision 5.6%. The plasma concentration—time profile was established after a single dose of 4 mg of dimethindene with an average maximum concentration of 5.5 ng/ml, detectable up to 48 h post application.

Determination of natural levels of coumarin in different types of tobacco using a mass fragmentographic method

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDetermination of natural levels of coumarin in different types of tobacco using a mass fragmentographic methodAlex. Christakopoulos, Kristina. Feldhusen, Harald. Norin, Ann. Palmqvist, and Inger. WahlbergCite this: J. Agric. Food Chem. 1992, 40, 8, 1358–1361Publication Date (Print):August 1, 1992Publication History Published online1 May 2002Published inissue 1 August 1992https://doi.org/10.1021/jf00020a014RIGHTS & PERMISSIONSArticle Views273Altmetric-Citations8LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (472 KB) Get e-Alerts Get e-Alerts

Simultaneous determination of sorbic acid, dehydroacetic acid and benzoic acid by gas chromatography-mass spectrometry

A method for the simultaneous determination of sorbic acid, dehydroacetic acid and benzoic acid using gas chromatographychemical ionization mass spectrometry is described. The three components were separated on diethylene glycol succinate and eluted in the order of sorbic acid, dehydroacetic acid and then benzoic acid. In chemical ionization, the multiple-ion monitor is set to the quasi-molecular ion, that is m/z 113 for sorbic acid, m/z 169 for dehydroacetic acid and m/z 123 for benzoic acid. The linear dynamic detection range was approximately 1 · 10 3 (5·10 −105·10 −7 g). The minimum detectable amounts of the three components were found to be 200−500 pg. The chemical ionization mass fragmentographic method was about ten-fold more sensitive than the electron impact method. This method was sensitive and selective without any influence of solvent peak and other contaminants. The method has been applied to the determination of preservatives in foods.

Measurement of 4 urinary C-18 oxygenated corticosteroids by stable isotope dilution mass fragmentography

The cortisol C-18 oxidation pathway leading to the production of 18-hydroxy-and 18-oxocortisol is expressed in adenomatous primary aldosteronism and glucocorticoid remediable aldosteronism. In order to better define the significance of the pathway and its usefulness in differential diagnosis, we have developed a stable isotope dilution mass fragmentographic method for the determination of the tetrahydro metabolites of aldosterone, 18-hydroxycorticosterone and 18-oxocortisol and of unmetabolized 18-hydroxycortisol in urine. Stereochemically correct tetrahydro steroids containing 3 deuterium atoms were synthesized from the available 3-keto-4-pregnenes in 2 steps and 1,2-deuterium-labeled 18-hydroxycortisol was prepared by selective deuteration of the 1,2-double bond of a dienone precursor. Simultaneous measurement of the 4 steroids permitted a comparison of the abnormal products of the C-18 oxidation of cortisol with the normal C-18 oxidation products of corticosterone, 18-hydroxycorticosterone and aldosterone. Application of the method to the definition of the normal range is described.

Gas chromatographic determination of N-acetylisoputreanine-γ-lactam, a unique catabolite of N 1-acetylspermidine

A capillary gas chromatographic method with nitrogen—phosphorus detection for the determination of N-acetylisoputreanine-γ-lactam (acisoga) in urine is described. The method was validated by comparing the results with those given by an isotope dilution mass fragmentographic method. Making use of specific inhibitors for copper-dependent amine oxidase and polyamine oxidase in rats, it was demonstrated that acisoga is formed by oxidative deamination of N 1-acetylspermidine by the former enzyme. Moreover, acisoga is not a substrate for pig liver polyamine oxidase. Increased concentrations of acisoga, relative to N 1-acetylspermidine, in urines of patients with non-Hodgkin's lymphoma indicated that this conversion diminishes the sensitivity of N 1-acetylspermidine as a marker for (tumour) cell death.

Mass fragmentographic determination of adamantanamines in tissues

A mass fragmentographic method for the determination of various 1-aminoadamantanes (A) in tissues taking advantage of the differential solubility of free aminoadamantanes and their hydrochlorides in heptane, 2 M NaOH and 0.1 M HCl for separation is described. As an internal standard a suitable analogue was used. After insertion of the samples into the mass spectrometer, under flush heating to 280° C the “area under the curve” values of the ion traces were used for calculation. The measurable adamantanamines as analytes vs. standards or vice versa are e.g.: D174 [2-(1-adamantyl)ethylamine] ( m/z 135 and 179) vs. D191 (3,5,7-trimethyl-A) ( m/z 122 and 193); D175 (3-ethyl-A) ( m/z 122 and 179) vs. D1 (A) ( m/z 94 and 151), etc.

Gas chromatography—mass spectrometry of perindopril and its active free metabolite, an angiotensin convertase inhibitor: choice of derivatives and ionization modes

Perindopril, a perhydroindole compound and a novel class of angiotensin convertase inhibitor, after oral administration leads to an active metabolite by de-esterification of an ethyl ester. Routine biological measurements are currently done using a radioimmunological assay, but a mass fragmentographic method was developed using plasma spiked with the drugs, which were then derivatized to the isobutyl ester heptofluorobutyramide and assayed using ammonia negative chemical ionization. Levels of 100 pg/ml were assayed. However, isobutanol derivatization provoked partial transesterification of the ethyl ester of the parent drug into the diisobutyl ester derivative, which corresponds to the active metabolite. A second method of derivatization to stable trimethylsilyl esters preserved the original ethyl ester of the parent drug. Despite the lower ionization yields, the mass fragmentographic method was sensitive and accurate enough to work satisfactorily at the 2 ng/ml level in spiked plasma, which is the level found currently in patients.

A new method for studying the incorporation of nonesterified fatty acids into cardiac lipids by using deuterium-labelled palmitate.

A new method for measuring the incorporation of exogenous fatty acids into myocardial lipids of working rat hearts using deuterium-labelled palmitate has been developed. After perfusing isolated hearts, the fatty acid composition of triglycerides, diglycerides, monoglycerides, cholesterol esters, and nonesterified fatty acids (NEFA) was measured by a mass fragmentographic method. Hearts perfused only with 5 mM glucose and 1 mM lactate perfusion as basic substrates showed a significant decrease of triglyceride content, while the other lipids were not found to be significantly reduced. The fatty acid composition of all lipids were not affected. An addition of D31-palmitate complexed to albumin at a molar ratio of 5:1, caused a dose-dependent incorporation into triglycerides and diglycerides which suggested saturation kinetics. The tissue content of nonesterified D31-palmitate was found to be linearly related to its concentration in the perfusate. It may be of note that the concentration of the other NEFA was significantly affected neither by a fatty-acid-free perfusion nor by a perfusion with D31-palmitate. A significant incorporation of the supplied fatty acid into cholesterol esters and monoglycerides could not be detected.

Simultaneous determination of trimipramine and its demethylated metabolites in plasma by gas chromatography-mass spectrometry

Abstract A capillary column gas chromatography—mass fragmentographic method for metapramine and its three major demethylated metabolites is described. Compounds are extracted from plasma using a double-extraction procedure and transformed into N-trifluoroacetyl derivatives. The detection is performed by monitoring specific ions for metapramine and for its metabolites with a mass detector. In spite of extensive metabolism in the liver and rapid elimination of metapramine, plasma concentrations of both metapramine and its metabolites can be simultaneously followed over 24 h after a single 150-mg oral dose, because of the sensitivity and selectivity of the method. This method has been successfully applied to the analysis of samples obtained from patients who were at steady state with metapramine and to a pharmacokinetic study in a healthy volunteer.

Mass fragmentographic determination of gamma-aminobutyric acid and glutamic acid in discrete amygdaloid nuclei of rat brain.

A mass fragmentographic method for the simultaneous quantification of gamma-aminobutyric acid (GABA) and glutamic acid is described. In a convenient one-step reaction, the two amino acids were derivatized with pentafluoropropionic anhydride and pentafluoropropanol. The derivatization products were stable for several days. The technique has been applied to the assay of GABA and Glu in five amygdaloid nuclei of the rat brain. The GABA level was high in the central and medial nuclei, whereas the Glu level was high in the lateral and basal nuclei. The regional distribution of GABA was different from that of Glu within the amygdaloid nuclei.

Histamine metabolism after adverse reactions due to d-tubocurarine administration.

We investigated histamine release in five female patients, submitted for gynaecological surgery, after intravenous administration of the neuromuscular blocking agent d-tubocurarine. In these patients, we measured the plasma levels of histamine and its metabolites, N tau-methylhistamine and N tau-methylimidazoleacetic acid, making use of mass fragmentographic methods. The newly developed determination of plasma N tau-methylimidazoleacetic acid had a within-day coefficient of variation of 2.7% (n = 10). Normal values of N tau-methylimidazoleacetic acid in plasma ranged from 41.3-75.6 nmol/l (n = 13). All five patients developed anaphylactoid reactions: two patients showed severe systemic reactions, one patient a minor systemic reaction and two had skin reactions only. Plasma histamine and N tau-methylhistamine levels appeared to be the most reliable biochemical parameters for confirming both the occurrence and severity of an anaphylactoid reaction. In comparison with plasma histamine, the determination of plasma N tau-methylhistamine is less hampered by artefacts caused by blood collection and plasma preparation. Together with the fact that the increase in plasma N tau-methylhistamine levels after anaphylactoid reactions lasts much longer than the increase in plasma histamine levels, this leads to the conclusion that the determination of plasma N tau-methylhistamine is a useful retrospective parameter for histamine release in this type of pathological state. The plasma N tau-methylimidazoleacetic acid levels fluctuated considerably, showing only a significant increase after administration of d-tubocurarine in the two patients who had severe anaphylactoid reactions. This parameter is, therefore, less useful in such studies.

Effect of age on homovanillic and 4-hydroxy-3-methoxymandelic acid levels in plasma.

The plasma levels of homovanillic and 4-hydroxy-3-methoxymandelic acids have been determined in 524 normal subjects ranging from birth to 49 years of age using a mass fragmentographic method. The mean concentration of homovanillic acid in plasma declines exponentially from the age of 1 day (X = 2342.0 nmol/l, 426.6 ng/ml) to adulthood (X = 60 nmol/l, 10.9 ng/ml). 4-Hydroxy-3-methoxymandelic acid behaves in a similar although not so extreme manner (392 nmol/l, 77.6 ng/ml-50 nmol/l, 10 ng/ml).

Increase in the Content of Quinolinic Acid in Cerebrospinal Fluid and Frontal Cortex of Patients with Hepatic Failure

Quinolinic acid (QUIN), an excitotoxic tryptophan metabolite, has been identified and measured in human cerebrospinal fluid (CSF) using a mass-fragmentographic method. Furthermore, its content has been evaluated in frontal cortex obtained at autopsy from the cadavers of patients who died after hepatic coma. During the coma, the concentration of QUIN in the CSF was 152 +/- 38 pmol ml-1. In contrast, the concentration in control patients affected by different pathologies was 22 +/- 7 pmol ml-1. In the frontal cortex of patients who died after episodes of hepatic encephalopathy, the content of QUIN was three times higher than in controls (2.6 +/- 0.6 versus 0.80 +/- 0.08 nmol/g wet weight). As a result of these investigations we are now able to extend our previous observations on the increase of QUIN in the brains of rats used as experimental models of hepatic encephalopathy to man. QUIN should therefore be added to the list of compounds possibly involved in the pathogenesis and symptomatology of brain disorders associated with liver failure.

Comparison of gas-liquid chromatography, mass fragmentography, and isotope dilution-mass spectrometry for determination of pentobarbitone in human plasma

Comparative studies of gas-liquid Chromatographic, mass fragmentographic methods, and isotope dilution-mass spectrometric assay for the quantitative determination of pentobarbitone in human plasma, are described. Butabarbitone is used as internal standard for the measurement of the drugs by gas-liquid chromatography and mass fragmentography, and deuterated pentobarbitone is used for quantification by the isotope dilution-mass spectrometric method.

Increased concentrations of the monoamine metabolities homovanillic acid and 5-hydroxyindoleacetic acid in lumbar and central CSF and of 3-methoxy-4-hydroxyphenylglycol in lumbar CSF after subarachnoid haemorrhage

The concentrations of the dopamine metabolite homovanillic acid (HVA), the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MOPEG) were determined in cerebrospinal fluid (CSF) from patients with subarachnoid haemorrhage (SAH) using a mass fragmentographic method. In a first group of 24 patients lumbar CSF was collected during the first 10 days after SAH. The concentrations of HVA and 5-HIAA showed a several-fold increase in the majority of subjects while that for MOPEG was less pronounced in comparison to controls. In a second group of 12 SAH-patients, CSF was collected in 10 ml fractions during surgical clipping of aneurysms. The mean concentrations of HVA, 5-HIAA and MOPEG in lumbar CSF was 469,275 and 39 pmol/l, respectively, whereas central CSF concentrations were 1,212, 499 and 48 pmol/ml, respectively. Compared to healthy controls, both HVA and 5-HIAA showed increased levels (pl 0,01) but MOPEG was within the normal range. No correlation between the concentrations of the monoamine metabolites, the neurological condition or the cerebral vascular diameter was observed in neither of the two groups. It is suggested that the accumulation of HVA and 5-HIAA in SAH patients is explained by a disturbance of the active transport mechanism.

Low HVA and normal 5HIAA CSF levels in drug-free schizophrenic patients compared to healthy volunteers: Correlations to symptomatology and family history

Cerebrospinal fluid (CSF) levels of homovanillic acid (HVA) and 5- hydroxyindoleacetic acid (5HIAA) were determined in 40 drug-free schizophrenic patients and 21 healthy volunteers by a mass fragmentographic method. Twenty-one of the schizophrenic patients were first admissions who had never received neuroleptics. Significantly, lower levels of HVA but not 5HIAA were found in the patient group, and no difference was found between chronic, previously neuroleptic-treated and never-medicated patients. HVA levels correlated positively with social interest and total positive scores on the Nurses Observation Scale for Impatient Evaluation (NOSIE-30) and negatively with lassitude and slowness of movements on the Comprehensive Psychopathological Rating Scale (CPRS). Low levels of 5HIAA were correlated to the CPRS items delusions and apparent sadness. There were slightly higher CSF levels of 5HIAA in patients with a family history of schizophrenia, but no such difference was seen for HVA. In both schizophrenic and control subjects CSF levels of HVA and 5HIAA showed a strong intraindividual correlation. The results indicate decreased central nervous system dopaminergic turnover in schizophrenia which seems to be associated with “negative” symptomatology.

Simultaneous determination of metapramine and its demethylated metabolites in plasma by gas chromatography—mass spectrometry

A capillary column gas chromatography—mass fragmentographic method for metapramine and its three major demethylated metabolites is described. Compounds are extracted from plasma using a double-extraction procedure and transformed into N-trifluoroacetyl derivatives. The detection is performed by monitoring specific ions for metapramine and for its metabolites with a mass detector. In spite of extensive metabolism in the liver and rapid elimination of metapramine, plasma concentrations of both metapramine and its metabolites can be simultaneously followed over 24 h after a single 150-mg oral dose, because of the sensitivity and selectivity of the method. This method has been successfully applied to the analysis of samples obtained from patients who were at steady state with metapramine and to a pharmacokinetic study in a healthy volunteer.

Rapid gas chromatographic—mass spectrometric quantitation of γ-aminobutyric acid in biological specimens

A mass fragmentographic method for γ-aminobutyric acid (GABA) quantitation using the heptafluorobutyryl-cyclohexyl-GABA derivative is described. Both capillary and packed column gas chromatography were used. This procedure employs 2,2[ 2H 2] GABA as an internal standard and allows the rapid, sensitive, and specific measurement of GABA with a minimum of sample clean-up. Application of the method is demonstrated in mouse embryonic brain, body, and palate and human platelets, plasma, cerebrospinal fluid, and urine.