QUANTITATIVE-DETERMINATION OF PENTAERYTHRITYL TETRANITRATE AND ITS METABOLITES IN HUMAN PLASMA BY GAS-CHROMATOGRAPHY MASS-SPECTROMETRY

Citation
D. Stalleicken et al., QUANTITATIVE-DETERMINATION OF PENTAERYTHRITYL TETRANITRATE AND ITS METABOLITES IN HUMAN PLASMA BY GAS-CHROMATOGRAPHY MASS-SPECTROMETRY, Arzneimittel-Forschung, 47(4), 1997, pp. 347-352
Citations number
31
Categorie Soggetti
Pharmacology & Pharmacy",Chemistry
Journal title
ISSN journal
00044172
Volume
47
Issue
4
Year of publication
1997
Pages
347 - 352
Database
ISI
SICI code
0004-4172(1997)47:4<347:QOPTAI>2.0.ZU;2-A
Abstract
Up to now, there has been no data available on the pharmacokinetics of pentaerythrityl tetranitrate (PETN, CAS 78-11-5) and its metabolites, pentaerythrityl-trinitrate (PE-tri-N), pentaerythrityl-dinitrate (PE- di-N), pentaerythrityl-mononitrate (PE-mono-N) in human plasma. Theref ore, in order to determine PETN and its metabolites in plasma sensitiv e and highly selective GC/MS methods had to be developed and validated . PETN and its metabolite PE-tri-N were validated in the concentration range 50 pg/ml to 10 ng/ml. Isosorbide dinitrate (ISDN) was used as t he internal standard and the analytes were extracted with dichlorometh ane from the plasma. The mass spectrometric tests were carried out usi ng chemical ionization in the negative mode (NlCl) with the applicatio n of ammonia as a reagent gas. The nitrate ion m/z 62 was determined i n the analytes and internal standard. The accuracy of the mean of the quality control samples during the three days (between days) was betwe en 100 and 110 % (PETN), as well as 90 and 106 % (PE-tri-N). After an oral application of 100 mg PETN in a pilot study, unchanged PETN and P E-tri-N was measured in plasma. Both metabolites PE-di-N and PE-mono-N were validated at the concentration range of 0.25 ng/ml to 25 ng/ml p lasma. After extraction, these analytes were derivatized with BSTFA (N ,O-bis[trimethylsilyl]trifluoro-acetamide). The applied internal stand ard was isosorbide-5-mononitrate (IS-5-MN). The mass spectrometric tes ts were carried out in the same manner as for PETN and PE-tri-N with c hemical ionization in the NlCl mode. The detected masses were m/z 324 for PE-di-N, m/z 351 for PE-mono-N and m/z 217 for IS-5-MN. The accura cy of the mean of the quality control samples during 5 days were betwe en 104 and 107 % (PE-di-N) and 102 and 106 % (PE-mono-N). The maximum concentration of these analytes in the subject samples were on the ave rage all over 5 ng/ml plasma after the oral administration of 100 mg P ETN.