Solid-phase column chromatographic and gas chromatographic-mass spectrometric determination of heptaminol in human urine and related pharmacokinetic profiles.

Heptaminol is an antihypotensive drug and is one of the stimulants banned in sport competitions. When heptaminol was fortified to a drug-free urine sample and subjected to solid-phase extraction, trifluroacetic anhydride derivatization, and gas chromatography-mass spectrometry analysis, the results indicated three chromatographic peaks, with one major peak [peak 1 (P1) as heptaminol-2TFA], appearing at retention time 7.17 min, and two minor peaks [peak 2 (P2) and peak 3 (P3) as heptaminol-TFA], appearing at RT 5.87 and 5.81 min, respectively. The characteristic ions of peak mass spectra were m/z 322, 224, and 140 for P1, m/z 223 (molecular ion), 208, 140, and 110 for P2, and m/z 208, 140, and 110 for P3. The urine samples collected from healthy male volunteers who orally ingested a single dose (100 mg) of heptaminol were similar to the analytical results shown in the heptaminol-spiked control urine samples. This result suggested that the unchanged heptaminol was the sole form found in urine. The unchanged parent compound was completely eliminated in urine within 24 h and an average of approximately 97% of the dose was excreted through the renal pathway.

Measurement of lymphatic flow variation by noninvasive method cases of lymphedema.

The purpose of this study was to measure the variations of lymphatic flow. A noninvasive isotopic method was used to achieve a functional exploration of lymphatic circulation. Fifteen subjects were used in the study: 10 healthy subjects and 5 patients with lower extremity lymphedema. A first subcutaneous injection of technetium 99m rhenium sulfate (99mTc) was performed in the first interdigital space of both feet. The radioactivity was recorded in two places: the first one on the inguinal site by a gamma camera; the second, below the first, on the precordial site by a multichannel analyzer. With the two types of recording procedures, it was possible to obtain a curve that showed the amount of radioactivity in relation to time. In order to obtain a muscular activity fifty-five minutes after the injection, each subject or patient spent ten minutes on an ergometric bike. A second subcutaneous injection was performed one week later, but prior to the injection, the subject or patient took orally 1800 mg of heptaminol adenosine phosphate (HAP) per day for three days. The radioactivity recording was made under the same conditions as with the muscular activity. The statistical results of the experiment without treatment on the two types of recording show that in the healthy subjects the amount of radioactivity increased during muscular activity. Moreover, the treatment indicated higher radioactivity values, which remained at a higher level. However, the muscular activity performed by a patient was unable to increase the radioactivity. On the other hand, the drug gave radioactivity values that were higher than the previous values of the first curve.(ABSTRACT TRUNCATED AT 250 WORDS)

Liquid chromatographic assay of heptaminol in serum and its oral pharmacokinetics in the dog.

In order to investigate the pharmacokinetics of heptaminol in dogs, a high-performance liquid chromatographic assay of the drug was devised and it was evaluated in a general purpose validation design through analysis of variance. Heptaminol and its internal standard n-propylamine were salted out from plasma together with acetonitrile, the previously proposed "solvent demixing " extraction procedure. Both amines were derivatised in acetonitrile with the o-phthaldialdehyde, 2-mercaptoethanol procedure of Roth. The adducts were quantitated by reversed-phase high-performance liquid chromatography on Radial-Pak cartridges with ultraviolet detection. Peak height ratios were linearly related to concentrations up to 250 mumol l-1 with a 2% coefficient of variation. Sensitivity was 3.5 mumol l-1 (signal-to-noise ratio of 5). Means of the usual pharmacokinetic parameters in four dogs were: elimination half-life 3.75 h, apparent distribution volume 2.18 l kg-1 and total clearance 0.402 l kg-1 h-1, similar to the results obtained in humans by other authors using radiolabelled heptaminol .