1. The pharmacokinetics of the two enantiomers of terbutaline, (+)T and (‐)T, and the racemate (+/‐)T, have been evaluated after single intravenous and oral dosage to six healthy volunteers. 2. The mean systemic clearance, CL, was 0.19 and 0.13 l h‐1 kg‐1 for (+)T and (‐)T, respectively. This difference was statistically significant. The mean clearance of (+/‐)T was 0.20 l h‐1 kg‐1. Volumes of distribution were similar (1.9 l kg‐1) after the three intravenous administrations. The differences in CL were reflected in values of the elimination half‐life and MRT. 3. The difference in CL of the isomers could be explained by a corresponding difference in their renal clearance, CLR. Competition for stereoselective active reabsorption in the tubule might explain why (+)T seemed to enhance the CLR of (‐)T when the drug was given as the racemate. 4. Oral bioavailability, calculated from plasma data, of (+)T was 7.5% and that of (‐)T was 14.8%. This difference was statistically significant and was mainly due to a difference in absorption of (+)T and (‐)T, but also to a difference in their subsequent first‐pass metabolism. The bioavailability of (+/‐)T was similar to that of (‐)T. 5. (‐)T appears to govern the absorption properties of the racemate, while (+)T determines its elimination behaviour. Systemic metabolism of the two enantiomers was similar and, therefore, a greater first‐pass metabolism of (+)T would reflect a higher capacity of the gut wall to metabolise this isomer.

Model melanins, synthesized with different cysteinyldopamine/dopamine ratios in the incubates, were oxidized with KMnO4 and the resulting compounds were analyzed by HPLC. The ratios between a phaeomelanin‐derived compound, thiazole‐4,5‐dicarboxylic acid (TDCA), and a compound derived from eumelanin, pyrrole‐2,3,5‐tricarboxylic acid (PTCA), reflected the composition of the model melanins. The neuromelanin of the human substantia nigra was isolated, and the pigment, as well as intact brain tissue from human substantia nigra was oxidized with KMnO4 and the TDCA/PTCA ratios were determined. Analysis of the isolated neuromelanin showed it to contain 2.3% sulfur and 8.1% nitrogen. The sulfur content indicates the pigment is a mixed‐type melanin, and the TDCA/PTCA ratio indicates that it consists of units derived from benzothiazines and from indoles in about equal amounts.

(22R,S)Budesonide was isolated from human plasma by solid-phase extraction. Switching from reversed-phase conditions during sample application and washing to normal-phase conditions during elution afforded a very clean extract. Budesonide was derivatized with acetic anhydride to form the 21-acetyl derivative before analysis by reversed-phase liquid chromatography combined with thermospray mass spectrometry. Deuterium-labelled budesonide was used as internal standard. Standard samples prepared in human albumin solution were used for the calibration curve. An automated liquid chromatography/mass spectrometry system, allowing unattended overnight operation, was used for routine analysis. The recovery of budesonide from plasma was 88.9 +/- 5.9% (mean +/- SD) and the method was linear over the range 0.30-30 pmol (amount analysed), corresponding to plasma concentrations of 0.10-10 nmol l-1. Budesonide could be measured down to 0.10 nmol l-1 with a within-day variation of 10-18% (CV). The error was less than +/- 15% at 0.10 nmol l-1 and less than +/- 7% at concentrations of 0.20 nmol l-1 or higher. The total imprecision between days was 9% (CV) at a concentration of 0.30 nmol l-1.

(R,S)-Bambuterol was isolated from plasma and urine by solid-phase extraction and analysed as its trimethylsilyl derivative by gas chromatography/chemical ionization mass spectrometry with ammonia as the reagent gas. Deuterium-labelled bambuterol was used as internal standard. An esterase inhibitor was added to plasma to prevent hydrolysis of bambuterol in the plasma sample. Bambuterol could be measured in plasma down to 1 nmol l-1 with a within-day variation of less than 5% (coefficient of variation). The lower limit of measurement in urine was judged to be 8 nmol l-1, a concentration at which the within-day variation was 5.4% (coefficient of variation).

Information on the composition of melanins is obtained by analysis both of 4-amino-3-hydroxyphenylalanine (AHP) after hydriodic acid degradation and of pyrrole-2,3,5-tricarboxylic acid (PTCA) after potassium permanganate oxidation. Analysis of thiazole-4,5-dicarboxylic acid (TDCA) and pyrrole-2,3-dicarboxylic acid (PDCA) after permanganate oxidation, provides additional information on the composition, TDCA on pheomelanin residues, and PDCA on indolic residues without carboxy groups. Using model melanins formed from dopa and cysteinyldopa in different proportions, we found the TDCA/(PTCA+PDCA) ratio to yield a reliable estimate of the relative proportions of pheomelanin and eumelanin. The PDCA/PTCA ratio reflects the relationship between indole residues with and without carboxy groups. We have analyzed degradation products from cultures of IGR 1, an extensively studied melanoma cell line. Cell cultures were harvested after 2, 4, and 7 days. Culture media were changed after 2 days in all series, and also after 4 days in one series harvested at 7 days. Cells without medium change had seven times the amount of melanin found in cultures with medium change. The PDCA/PTCA ratio decreased with increasing amounts of melanin. With increased melanization, eumelanin is increased relatively more than pheomelanin. The cell content of 5-S-cysteinyldopa (5-S-CD) was similar in all cultures, while 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MICA), a eumelanin precursor metabolite, was found in increased amounts of media of heavily pigmented cultures.