AbstractAn experiment based on a 33 design has been undertaken to establish the effect on drug release from capsules produced by adding lactose (0, 10 and 50%), magnesium stearate (0, 1 and 5%), and sodium lauryl sulphate (0, 1 and 10%) to a 76–105μm particle size fraction of ethinamate filled into capsules at a high and low packing density. Statistical analysis of the results indicated the presence of 2nd order interaction at all time intervals and for both sets of capsule fill weights. This signifies that the effect produced by each additive is dependent on the presence and the level of the other two additives. The interaction limits the conclusions that can be drawn about the main factors of diluent, lubricant and wetting agent, but the indications are that (a) 10% diluent reduces drug release, whereas 50% produces enhanced release; (b) the presence of 1% sodium lauryl sulphate is sufficient to enhance drug release; (c) the additive effects are independent of the capsule packing density.

1992-12-15·The Journal of biological chemistry

Inhibition of carbonic anhydrases I and II by N-unsubstituted carbamate esters.

Article

作者: Parr, J S ; Khalifah, R G

We previously showed that the zinc metalloenzyme carbonic anhydrases (CA I and II isozymes) bind "neutral" amides and related compounds as anions through coordination of their deprotonated amide nitrogen to the active site zinc (Rogers, J. I., Mukherjee, J., and Khalifah, R. G. (1987) Biochemistry 26, 5672-5679). Urethan, the ethyl carbamate ester, was among such compounds. The present study was designed to test whether other N-unsubstituted carbamate esters of pharmacological interest (as sedatives, hypnotics, anxiolytics, and skeletal muscle relaxants) were capable of binding to CA in the same manner. We studied the interaction of human CA I and II with urethan, phenyl carbamate, ethinamate, meprobamate, and methocarbamol. Phenyl carbamate studies were greatly complicated by its uncatalyzed hydrolysis via an elimination mechanism to form cyanate, a powerful CA inhibitor. In general, the compounds display: 1) slow on-off inhibition binding kinetics in the seconds range, 2) maximal inhibitor affinity at alkaline pH, and 3) characteristic three-band visible spectra of their complexes with cobalt-substituted CA I. These properties are shared with the previously studied amide inhibitors and are taken as evidence that the deprotonated carbamate nitrogen coordinates to the active site metal ion. CA I appeared to bind carbamate esters more tightly than CA II, an unusual 1000-fold selectivity being seen in the case of methocarbamol. The inhibition by these drugs is not sufficiently strong to implicate CA I and II in their mechanism of action. However, it does suggest the possible existence of previously unsuspected similarities between binding to CA and to their physiological receptors or targets, particularly the involvement of zinc.

1990-01-01·Journal of Chromatography B: Biomedical Sciences and Applications

Identification and differentiation of barbiturates, other sedative-hypnotics and their metabolites in urine integrated in a general screening procedure using computerized gas chromatography-mass spectrometry

Article

作者: Maurer, H H

A gas chromatographic-mass spectrometric procedure is described for the identification and differentiation of sedative-hypnotics and their metabolites in urine. The following 24 barbiturates and thirteen other hypnotics could be detected: acecarbromal, allobarbital, amobarbital, aprobarbital, barbital, brallobarbital, bromisoval, (sec)butabarbital, butalbital, butobarbital, carbromal, clomethiazole, crotylbarbital, cyclobarbital, cyclopentobarbital, diethylallylacetamide, dipropylbarbital, glutethimide, guaifenesin, ethinamate, heptabarbital, hexobarbital, meprobamate, methaqualone, metharbital, methohexital, methylphenobarbital, methyprylone, pentobarbital, phenobarbital, propallylonal, pyrithyldione, secobarbital, thiobutabarbital, thiopental, vinbarbital and vinylbital. The procedure presented is integrated in a general screening procedure (general unknown analysis) for several groups of drugs detecting over 300 drugs and over 1000 of their metabolites. It includes cleavage of conjugates by acid hydrolysis, isolation by liquid-liquid extraction, derivatization by acetylation, separation by capillary gas chromatography, and identification by computerized mass spectrometry. Using mass chromatography with the selected ions m/z 83, 117, 141, 167, 169, 207, 221 and 235, the presence of barbiturates, other hypnotics and/or their metabolites was indicated. The identity of positive signals in the reconstructed mass chromatograms was confirmed by a visual or computerized comparison of the stored full mass spectra with the reference spectra. The sample preparation, mass chromatograms, reference mass spectra and gas chromatographic retention indices are documented.

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