GLC Determination of Nitroglycerin and Isosorbide Dinitrate in Human Plasma

Rosseel, M. T.; Bogaert, M. G.

doi:10.1002/jps.2600620510

Cited by 95 publications

(17 citation statements)

References 10 publications

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“…Each specimen was collected in an anticoagulant tube, quickly centrifuged and the plasma decanted and quick-frozen. The technique of gas-liquid chromatography with electroncapture detection, as described by Rosseel & Bogaert (1973) Figure 1 shows in graphic form the plasma concentrations of ISDN, 2-ISMN and 5-ISMN in a patient (T.T. ), whose daily dose of ISDN was 360 mg.…”

Section: Methodsmentioning

confidence: 99%

Plasma concentrations of isosorbide dinitrate and its metabolites after chronic high oral dosage in man.

Shane¹,

Iazzetta²,

Chisholm³

et al. 1978

Brit J Clinical Pharma

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I We have previously reported that vasodilator headache due to isosorbide dinitrate (ISDN) can be circumvented by using small 'priming' doses for an induction period of 1-2 weeks, after which it is possible to increase to dose rapidly to 360-720 mg, daily without recurrence of headache and without toxicity. The present study corroborates this earlier finding. 2. Chronic oral administration of doses of ISDN of this order of magnitude results in prolonged high plasma concentrations of the parent compound, as well as higher levels of the metabolites 2-ISMN and 5-ISMN. 3. It is our thesis that chronic high oral dosage of ISDN saturates the intrahepatic biotransformation process, and allows high concentrations of ISDN and its metabolites to enter the systemic circulation.

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Section: Methodsmentioning

confidence: 99%

Plasma concentrations of isosorbide dinitrate and its metabolites after chronic high oral dosage in man.

Shane¹,

Iazzetta²,

Chisholm³

et al. 1978

Brit J Clinical Pharma

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“…Therefore, it is of great interest to measure plasma levels of all three compounds together, but only few methods have been yet described In five procedures, conventional pack.ed column GLC was used, however, neither of these assays led to satisfactory sensitivity and selectivity. Large sample volumes (3-5 ml) are required [8,11,12] and difficulties occurred with the [8-141. quantitative mononitrate determination due to peak interferences, mainly by IS-5-MN [l 11. In two assays no internal standard was used [10,11].…”

Section: Introductionmentioning

confidence: 99%

Improved automated simultaneous determination of isosorbide dinitrate and its metabolites in plasma by capillary column gas chromatography

Rasper

Gielsdorf

et al. 1984

J. High Resol. Chromatogr.

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SummaryAn automated specific and sensitive method for the simultaneous determination of isosorbide dinitrate and its metabolites isosorbide-2-mononitrate, isosorbide-5-mononitrate, isomannide mononitrate, and isoidide mononitrate at concentrations down to 0.5,1,3,2, and 2 nglml, respectively, in human plasma is described. The procedure involves the extraction of the drug and its metabolites together with their internal standards isomannide dinitrate and o-nitrobenzyl alcohol from plasma with dichlorornethane.The analysis iscarried out by fused silica capillary gas chrornatography using a 63Ni-electron capture de1,ector. The method is applied to the pharmacokinetics of isosorbide dinitrate in humans.

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“…Supernatant plasma (3 ,ul) was transferred to a 10 ml capacity glass tube and 10 ,ul of 25 ng/ml y-lindane in hexane were added to each sample as internal standard. Hexane was used instead of ethylacetate as previously described (Rosseel & Bogaert, 1973) because it is more easily purified and was found to extract fewer unwanted plasma constituents. y-lindane was used instead of isosorbide dinitrate as previously described (Rosseel & Bogaert, 1973;Yap et al, 1978;Armstrong et al, 1979) because it is more soluble in hexane and has a shorter retention time.…”

Section: Protocolmentioning

confidence: 99%

Pharmacokinetic studies of various preparations of glyceryl trinitrate.

Bashir¹,

Mj²,

Henderson³

1982

Brit J Clinical Pharma

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1 The pharmacokinetics and pharmacodynamics of five pharmaceutical preparations of glyceryl trinitrate (GTN) have been studied in six healthy volunteers. 2 Peak plasma GTN levels of 1.4 + 0.1 ng/ml were achieved at 3 min after sublingual administration (0.5 mg); 2.8 + 0.6 ng/ml and 2.5 + 0.3 ng/ml at 2 h and 4 h after Nitrocontin (6.4 mg) and Sustac (6.4 mg) respectively; 2.7 + 0.1 ng/ml and 2.5 ± 0.2 ng/ml at 30 min after the cream (23 mg) and ointment (35 mg) respectively. 3 The mean times to reach half peak plasma GTN levels were 4.2 + 0.7 min after sublingual GTN, 6.5 + 0.9 h after Nitrocontin, 4.1 + 0.7 h after Sustac, 46.1 + 10.2 min after the ointment and 50.2 ± 39.2 min after the cream. 4 Plasma nitrate (NO3) levels were undetectable after sublingual administration; peak NO3 levels were 0.48 + 0.03 ,ug/ml at 4 h after Nitrocontin, 0.45 + 0.02 ,ug/ml at 6 h after Sustac, 0.68 + 0.04 ,g/ml at 6 h (end of study) after the ointment and 0.63 ,ug/ml at 4 h after the cream. 5 Plasma nitrite (NO2) was undetectable after sublingual GTN and peak NO2 levels were 0.48 ± 0.04 ,ug/ml at 2 h after Nitrocontin, 0.48 + 0.02 ,ug/ml at 2 h after Sustac, 0.69 ± 0.02 jug/ml at 1 h after the ointment and 0.64 + 0.02 ,ug/ml at 1 h after the cream. 6 Blood pressure (BP) declined throughout the 11 min of the study after sublingual GTN but did not change significantly after Nitrocontin or Sustac. After the ointment and the cream BP fell to the lowest level 30-60 min after administration and remained low throughout the 6 h of the study. 7 Heart rate (HR) increased to a maximum 5 min after sublingual administration with no significant increase after Nitrocontin or Sustac. After the ointment and the cream HR increased gradually to a maximum 30-60 min after administration remaining high throughout the rest of the study.

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GLC Determination of Nitroglycerin and Isosorbide Dinitrate in Human Plasma

Cited by 95 publications

References 10 publications

Plasma concentrations of isosorbide dinitrate and its metabolites after chronic high oral dosage in man.

Plasma concentrations of isosorbide dinitrate and its metabolites after chronic high oral dosage in man.

Improved automated simultaneous determination of isosorbide dinitrate and its metabolites in plasma by capillary column gas chromatography

Pharmacokinetic studies of various preparations of glyceryl trinitrate.

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