Femtogram level quantitative determination of nitroglycerin and metabolites in human plasma by GC‐MS negative ion chemical ionization, single ion monitoring

Settlage, J. A.; Gielsdorf, W.; Jaeger, H

doi:10.1002/jhrc.1240060204

Cited by 26 publications

(9 citation statements)

References 33 publications

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“…Gas chromatography-mass spectrometry (GC-MS) with electron impact and, more recently, with negative-ion chemical ionisation leads to a very high sensitivity and specificity (Gaudry et al 1984;Settlage et al 1983). Limited data about the comparative value of GC-ECD and GC-MS are available Sioufi & Pommier 1985).…”

Section: Assay Methodsmentioning

confidence: 99%

Clinical Pharmacokinetics of Glyceryl Trinitrate Following the Use of Systemic and Topical Preparations

Bogaert

1987

Clinical Pharmacokinetics

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Glyceryl trinitrate has been used for more than a century for the treatment of angina pectoris and, more recently, for the treatment of congestive heart failure. The introduction of transdermal delivery systems has renewed the controversy regarding the efficacy of the drug, mainly in the light of the development of tolerance. With concentrations of the order of 1 microgram/L or less, the measurement of glyceryl trinitrate in plasma is not easy: gas chromatography with electron capture detection has been used widely but recently gas chromatography-mass spectrometry has provided satisfactory results. Assay problems are most likely to be responsible for some of the unexpected results reported. Further factors which may confound the results of the study of plasma concentrations are the rapid metabolism of glyceryl trinitrate in blood in vitro, adsorption to containers and infusion sets, and the uptake and/or metabolism in vessel walls. From the intravenous infusion data, the large interindividual variability in plasma concentrations of glyceryl trinitrate is apparent. The plasma half-life is about 2 to 3 minutes; plasma clearance values reported vary from 216 to 3270 L/h, indicating extensive non-hepatic metabolism. With transdermal administration, mainly with the transdermal controlled delivery systems, plasma concentrations of glyceryl trinitrate appear to be maintained for up to 24 hours, with large interindividual variations. Despite the ability to maintain, for example with the transdermal delivery systems, relatively constant concentrations of glyceryl trinitrate, it has not been possible to find a relationship between plasma concentrations and pharmacological or clinical effects. This is in part due to the attenuation of the effects with time; from the available data it is clear that this attenuation occurs at a pharmacodynamic level (reflex adaptation and tolerance) and not at the pharmacokinetic level.

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Section: Assay Methodsmentioning

confidence: 99%

Clinical Pharmacokinetics of Glyceryl Trinitrate Following the Use of Systemic and Topical Preparations

Bogaert

1987

Clinical Pharmacokinetics

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“…Assay was by gas chromatographymass spectrometry using a VG micromass 7035 mass spectrometer coupled to a Dani 3800 chromatograph. The method has been previously described by Settlage et al (1983).…”

Section: Methodsmentioning

confidence: 99%

Plasma levels of nitroglycerin generated by three nitroglycerin patch preparations, Nitradisc, Transiderm‐Nitro and Nitro‐Dur and one ointment formulation, Nitrobid.

McAllister¹,

Mosberg

Ja³

et al. 1986

Brit J Clinical Pharma

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Twenty‐four healthy male subjects participated in a study comparing plasma concentrations of nitroglycerin generated by single applications of Nitradisc 32 mg, Transiderm‐Nitro 50 mg and Nitro‐Dur 104 mg patches and from one inch of Nitrobid 2% ointment. The three patch preparations are designed to release 10 mg nitroglycerin systemically over a 24 h period. Nitrobid ointment is intended to deliver 15 mg nitroglycerin per inch of ointment, and to be reapplied at least every 8 h. Blood was taken for nitroglycerin assay up to and including 24 h after each application. Assay for nitroglycerin was performed using a gas chromatography‐mass spectrometry technique. Plasma concentrations of nitroglycerin were sustained up to the 24 h mark with all three patch preparations, but not with application of Nitrobid ointment. Nitrobid was associated with a rapid rise in nitroglycerin plasma concentrations maximal 1 h after application. Plasma concentrations of nitroglycerin absorbed from Nitrobid ointment fell below those absorbed from all three patch preparations after 8 h. Clinically, all four formulations were similar with respect to side effects, with headache and dizziness being the most common.

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“…Such high efficiency columns will also give higher sensitivity. Only two capillary GC (CGC) methods using negative ion chemical ionization mass spectrometry with single ion monitoring (NICI-SIM MS) have been reported [11,12]. The method developed by Miyasaki et a/.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous determination of glyceryl trinitrate and its metabolites in plasma using capillary gas chromatography with on‐column injection

Langseth-Manrique¹,

Bredesen²,

Greibrokk³

1986

J. High Resol. Chromatogr.

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A specific, sensitive, and precise assay for simultaneous quantitation of glyceryl trinitrate (GTN) and its metabolites 1,2and 1,3-glyceryl dinitrate (GDN) has been developed. The method involves one single extraction step with benzene, followed byevaporation at 55'C.One plof theextractwasinjected onto a capillary fused silica column with trifluoropropyl as the stationary phase.Thecolumnseparatedal1 thenitrateswithin 17 minutes using temperature programming from 90 to 155OC. The lower limits of detection were 0.05,0.5, and 0.1 nmol/l for GTN, 1,2-GDN and 1,3-GDN respectively. The calibration curves were linear in the concentration ranges 0.05-1 0.0 nmol/l (GTN), 0.5-10.0 nmol/l (1,2-GDN) and 0.1-10.0 nmol/l (1,3-GDN). Plasma concentration data from two patients receiving intravenous GTN infusion are presented.

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Femtogram level quantitative determination of nitroglycerin and metabolites in human plasma by GC‐MS negative ion chemical ionization, single ion monitoring

Cited by 26 publications

References 33 publications

Clinical Pharmacokinetics of Glyceryl Trinitrate Following the Use of Systemic and Topical Preparations

Clinical Pharmacokinetics of Glyceryl Trinitrate Following the Use of Systemic and Topical Preparations

Plasma levels of nitroglycerin generated by three nitroglycerin patch preparations, Nitradisc, Transiderm‐Nitro and Nitro‐Dur and one ointment formulation, Nitrobid.

Simultaneous determination of glyceryl trinitrate and its metabolites in plasma using capillary gas chromatography with on‐column injection

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