The anticonvulsant and toxic properties of 4-amino-N-(2,6-dimethylphenyl)benzamide, (ADD 75073), were compared with phenytoin (PHT), phenobarbital (PB), ethosuximide (ESM), and valproate (VPA). These compounds were evaluated in mice and rats using well-standardized anticonvulsant test procedures. The results indicate that ADD 75073 is a very potent anticonvulsant in the maximal electroshock seizure (MES) model. The compound was effective in nontoxic doses following intraperitoneal (i.p.) administration in mice and oral administration in both mice and rats. In mice, the i.p. administration of ADD 75073 resulted in an ED50 value of 2.6 mg/kg as compared with a value of 9.5 mg/kg for phenytoin (PHT) in the same assay. Compound ADD 75073 was ineffective in nontoxic doses against all other seizure models examined in this study, and thus has a pharmacologic profile similar to that of PHT.

The popular drug of abuse 3,4-methylenedioxymethamphetamine (MDMA) is one of a total of 10 regioisomeric 2,3- and 3,4-methylenedioxyphenethylamines of MW 193 that yields regioisomeric fragment ions with equivalent mass (m/z 58 and 135/136) in the electron-impact (EI) mass spectrum. Thus, these 10 methylenedioxyphenethylamines are uniquely isomeric; they have the same molecular weight and equivalent major fragments in their mass spectra. The specific identification of one of these compounds (i.e., Ecstasy or 3,4-MDMA) in a forensic drug sample depends upon the analyst's ability to eliminate the other regioisomers as possible interfering or coeluting substances. This study reports the synthesis, chemical properties, spectral characterization, and chromatographic analysis of these 10 unique regioisomers. The ten 2,3- and 3,4-regioisomers of MDMA are synthesized from commercially available precursor chemicals. In the EI mass spectra, the side-chain regioisomers show some variation in the relative intensity of the major ions, with the exception of only one or two minor ions that might be considered side-chain specific fragments. The position of substitution for the methylenedioxy ring is not easily determined by mass spectral techniques, and the ultimate identification of any one of these amines with the elimination of the other nine must depend heavily upon chromatographic methods. The chromatographic separation of these 10 uniquely regioisomeric amines are studied using reversed-phase liquid chromatographic methods with gradient elution and gas chromatographic techniques with temperature program optimization.

Triple-quadrupole mass spectrometry (MS/MS) has been used to compare nitroaromatic emissions from two different types of diesel engines, a direct-injection, single-cylinder engine and an indirect-injection V-8 engine. The low level of nitropyrenes/ nitrofluoranthenes in exhaust extracts may be due in part to the low pyrene content of the reference fuel used. Addition of pyrene to reference fuel resulted in increased pyrene in exhaust extracts, but only minor differences in mutagenicity. Only about 1/1000 of the total mutagenicity from complete reaction with N02 appeared to have occurred during diesel exhaust and soot collection on filters. Fractionation with Me2SO was found to be useful in separating aliphatic hydrocarbons from mutagenic activities and in concentrating nitroaromatic compounds for MS/MS analysis.Concentration of certain nitroaromatic compounds was necessary for isobutane chemical ionization MS/MS, while atmospheric pressure MS/MS appeared capable of detecting nitroaromatic compounds even in unfractionated extracts. MS/MS comparisons of concentrated samples of differing mutagenicities showed the main differences were increased ion intensities of dinitro compounds in more mutagenic samples. It is concluded that the polynitro compounds may be of more significance than mononitro compounds in the mutagenic activities that have been found associated with diesel soot.

A sensitive, specific urinary assay for fentanyl, sufentanil, and alfentanil based on their N-dealkylated metabolites is described. Norfentanyl, norsufentanil-noralfentanil, and 2H5-norfentanyl are synthesized and characterized by standard analytical techniques. Derivatization of these secondary amines to yield the pentafluorobenzamides produces stable products with good gas chromatographic properties and unique, high-mass fragments in their mass spectra. These properties are utilized to develop a drug screening procedure based on gas chromatography-mass spectrometry to detect these major metabolites in human urine. The metabolites are isolated from urine samples by a liquid-liquid extraction procedure. The method allows for detection of metabolite concentrations as low as 0.3 ng/mL.

The reversed-phase liquid chromatographic properties of N-hydroxy-3,4-methylenedioxyamphetamine (NOHMDA) were determined on a C8 stationary phase specifically prepared for the separation of basic compounds. NOHMDA and several N-alkyl MDA derivatives displayed excellent peak shape on this stationary phase without the need for competing bases such as triethylamine. The k' values for NOHMDA varied with mobile phase pH in the range of 2.5 to 6.0, but the retention of the primary amine, MDA, and N-alkyl MDAs remained relatively constant over this range. The pKa value for NOHMDA was determined by titration to be 6.22 compared to a pKa of 10.04 for MDA. Thus, the variation of k' with mobile phase pH for NOHMDA may be a result of appreciable changes in degree of protonation. The stability of NOHMDA was found to decrease with an increase in aqueous solution pH. At pH 7.0 the degradation half-life was determined to be 49.8 h, which decreased to 2.57 h at pH 10.0. Above pH 10.0 the decomposition to the corresponding oxime was too fast for a reliable half-life determination.