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

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.

Measurement of ergotamine in human plasma by triple sector quadrupole mass spectrometry with negative ion chemical ionization.

By use of negative ion chemical ionization and collision-activated decomposition in a triple quadrupole mass spectrometer a method has been developed for the quantification of ergotamine in human plasma at levels down to 2 pg ml-1.

Quantitative determination of bencyclane in human plasma by capillary gas chromatography/chemical ionization mass spectrometry.

Since 10 years there is a phenomenal increase in the use of mass spectrometry, combined with (capillary-) gas chromatography and dedicated data systems for the rapid, reliable, sensitive and selective determination of xenobiotics (drugs, their degradation/biotransformation products etc.) in biological fluids. This applies especially since the introduction of newer developments in ionization techniques (CI, DCI, FAB) and gas chromatographic column technology (fused silica, bonded phase columns). We employed such a sophisticated method for the quantitative determination of N-[3-(1-benzyl-cycloheptyl-oxy)-propoxy]-N,N'- dimethylammoniumhydrogen fumarate (bencyclane) in human plasma after oral application of a therapeutic doses. Our results clearly show that this approach is the best method available; furthermore the detected plasma levels will lead to discussions with respect to the pharmacokinetic properties of the drug.

[Bioavailability of glycerol trinitrate (nitroglycerin) from an ointment preparation]. / Bioverfügbarkeit von Glyceroltrinitrat (Nitroglycerin) aus einer Salbenzubereitung.

After application of an ointment of glycerol trinitrate (nitroglycerin, Nitrofortin; in the following briefly called GTN) the bioavailability of the unchanged GTN was evaluated. For that purpose a gas chromatographic/mass spectrometric method was employed, the only method which guarantees the selectivity and sensitivity necessary for this kind of studies. In this respect selectivity means that only the unchanged drug is determined and degradation and/or biotransformation products are measured only if needed. Considering the well-known tremendous inter-individual variations, which are quite common in studies with this compound, and the associated problems of getting statistically relevant data the study was performed on 12 volunteers. Detectable GTN-levels were obtained up to 48 h after application, maximum plasma levels (836.1 +/- 124.2 pg/ml) were reached after 1.37 +/- 1.55 h. 12 h after application plasma concentrations of 154 +/- 20 pg/ml were observed which decreased to 65 +/- 13 pg/ml after 24 h.

[Gas chromatographic/mass spectrometric determinations of indomethacin serum levels in the course of pharmacokinetic studies in healthy volunteers]. / Die gaschromatographisch/massenspektrometrische Bestimmung der Indometacin-Serumspiegel im Verlauf pharmakokinetischer Untersuchungen an gesunden Freiwilligen.

For 4 different brands of indomethacin preparations the in vitro dissolution data as well as their relative bioavailabilities were determined. The in vitro tests were performed by the rotating basket method; the quantitative determinations of the serum-levels were determined by an gas chromatographic/mass spectrometric assay employing registration of the characteristic selected ion current profiles of the compound. Furthermore a special method for synthesis of the needed internal standard was also developed. The in-vivo-studies - with 15 volunteers in a 4 fold crossover-showed - in contrast to the worse in-vitro-dissolution of one preparation - bioequivalency of all four preparations. Our results clearly show that statements on in-vitro/in-vivo correlations have to be cautious.