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
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.