Jack DeRuiter

Liquid chromatographic and mass spectral analysis of N-substituted analogues of 3,4-methylenedioxyamphetamine

The C1 to C3 N-alkyl, N,N-dimethyl, and N-hydroxy analogues of 3,4-methylenedioxyamphetamine (MDA) are identified by high performance liquid chromatographic (HPLC) and spectrometric techniques. The compounds are separated using reversed-phase procedures on C18 stationary phase with an acidic (pH 3) aqueous methanol mobile phase. The mass spectra of the compounds are distinctive and reference spectra are provided. The N-hydroxy derivative is unstable at high temperatures and decomposes to MDA and the oxime of 3,4-methylenedioxyphenyl-2-propanone.

GC-IRD methods for the identification of isomeric ethoxyphenethylamines and methoxymethcathinones

A series of 12 isomeric phenethylamines were evaluated by gas chromatography using vapor phase infrared spectrophotometric detection. The major mass spectral fragments for each of these unique isomers occur at equivalent mass and all have equal molecular weight. The infrared spectra for these compounds allow for identification of any one of these amines to the exclusion of all other isomers. This differentiation is accomplished without the need for chemical derivatization. The methoxymethcathinones show unique infrared absorption bands in the 1690-1700 cm(-1) range for the carbonyl group and the ring substitution pattern in the ethoxymethamphetamines can be differentiated by several bands in the 700-1610 cm(-1) region. Side chain and degree of nitrogen substitution can be evaluated in the 2770-3000 cm(-1) region of the infrared range. All the studied regioisomers could be differentiated from 3,4-MDMA via their vapor phase IR spectra. Capillary gas chromatography on an Rxi-50 stationary phase successfully resolved the side chain regioisomers, the substituted methamphetamines and the methoxymethcathinones.

A Biodegradable Injectable Implant Sustains Systemic and Ocular Delivery of an Aldose Reductase Inhibitor and Ameliorates Biochemical Changes in a Galactose-Fed Rat Model for Diabetic Complications

AbstractPurpose. To fabricate and characterize in vitro and in vivo performance of a sustained release biodegradable implant for N-4-(benzoylaminophenylsulfonyl glycine) (BAPSG), a novel aldose reductase inhibitor. Methods. The ability of BAPSG to inhibit aldose reductase activity and glucose-induced vascular endothelial growth factor (VEGF) expression was assessed in a retinal pigment epithelial cell line (ARPE-19). A poly (DL-lactic-co-glycolic acid) implant containing 50% w/w BAPSG was fabricated and characterized for drug loading, in vitro drug release, and the thermal behavior of the drug and the polymer. Implants were injected subcutaneously into a galactose-fed diabetic rat model and cataract scores, plasma and tissue drug levels, galactitol levels in the lens and the retina, glutathione levels in the plasma, lens, cornea and retina and VEGF expression in the retina were determined on or until 18 days. Results. BAPSG inhibited aldose reductase activity and reduced VEGF expression in ARPE-19 cells. Implants (1 × 4 mm), with a loading efficiency of 106 ∓ 7% for BAPSG, were fabricated. Upon implant fabrication, while the glass transition temperature of the polymer decreased, the melting point of the drug was not affected. In vivo drug release correlated well with in vitro release, with ≈44% drug release occurring in vivo by the end of 18 days. The implant reduced galactitol accumulation, glutathione depletion, cataract scores, and VEGF expression in galactose-fed rats. Conclusions. An injectable biodegradable implant of BAPSG sustained drug release in vitro and in vivo, and reduced galactitol accumulation, glutathione depletion, cataract scores, and VEGF expression in galactose-fed rats.

Effects of designer drugs on the chicken embryo and 1-day-old chicken.

The present study was conducted to examine the effects of d-amphetamine and the designer drugs 3,4-methylenedioxymethamphetamine (MDMA), N-methyl-3,4-methylenedioxyphenyl-3-butamine (HMDMA), 3,4-methylenedioxyphenyl-2-butanamine (BDB), 3,4-methylenedioxyphenyl-1-ethanamine (MDM1EA) in the chick embryo and the young chicken. HMDMA and MDM1EA had no effect on motility on day 14 of embryogenesis, while MDMA, BDB, and d-amphetamine decreased embryonic motility at one or more doses. On day 1 posthatch, chickens were challenged with cumulative injections of water or the same drug that they had received in ova. With the exception of MDM1EA, all of the drugs produced effects such as distress vocalization, wing extension, tremor, flat body posture, bursting forward movements, loss of righting reflex, and convulsant-like kicking. Pretreatment with drug in ova resulted in tolerance to certain drug effects and supersensitivity to other drug effects. Furthermore, BDB significantly decreased hatchability, MDM1EA decreased body weight, and HMDMA decreased liver weight. Further studies are needed to determine the mechanism(s) of toxicity in this species.

GC–MS studies on acylated derivatives of 3-methoxy-4-methyl- and 4-methoxy-3-methyl-phenethylamines: Regioisomers related to 3,4-MDMA

A series of side chain regioisomers of 3-methoxy-4-methyl- and 4-methoxy-4-methyl-phenethylamines have mass spectra essentially equivalent to the controlled drug substance 3,4-methylenedioxymethamphetamine (3,4-MDMA), all have molecular weight of 193 and major fragment ions in their electron ionization mass spectra at m/z 58 and 135/136. The acetyl, propionyl and trifluoroacetyl derivatives of the primary and secondary regioisomeric amines were prepared and evaluated in GC-MS studies. The mass spectra for these derivatives were significantly individualized and the resulting unique fragment ions allowed for specific side chain identification. The trifluoroacetyl derivatives provided more fragment ions for molecular individualization among these regioisomeric substances. These trifluoroacetyl derivatives showed excellent resolution on a non-polar stationary phase such as Rtx-1.

Comparison of GC–MS and GC–IRD methods for the differentiation of methamphetamine and regioisomeric substances

Gas chromatography-mass spectrometry (GC-MS) and gas chromatography-infrared detection (GC-IRD) methods were developed and compared for the differentiation of regioisomeric phenethylamines related to methamphetamine. There are a total of five regioisomeric phenethylamines (methamphetamine and four regioisomers) that produce essentially equivalent mass spectra. This unique set of five phenethylamines having the same molecular weight and elemental composition yield major mass spectral fragments at equivalent mass. The trifluoroacetyl derivatives of the primary and secondary amines yield characteristic individual fragment ions allowing structural differentiation among these regioisomers. The vapor phase infrared spectra generated via capillary gas chromatography differentiated among these compounds without the need for derivatization. The regioisomeric phenethylamines are well resolved by GC with the elution order generally determined by the degree of molecular linearity.

Studies on aldose reductase inhibitors from fungi. I. Citrinin and related benzopyran derivatives.

The fungal metabolites, citrinin (4,6-dihydro-8-hydroxy-3,4,5-trimethyl-6- oxo-3H-2-benzopyran-7-carboxylic acid) and DHMI (3,4-dihydro-6-methoxy-3,7-dimethyl-1H-2-benzopyran-8-ol), as well as certain synthetic derivatives, have been evaluated for aldose reductase inhibitory activity using a rat lens enzyme preparation. Citrinin and its reduction product, dihydrocitrinin, were found to have significant activity (IC50 approximately 10 microM), whereas the other compounds were 3-10 times less potent. Kinetic studies showed that citrinin was not an irreversible inhibitor of the enzyme, as might be expected of a quinone methide. Spectroscopic (NMR) evidence is presented for the existence of citrinin predominantly in the form of its hemi-acetal in aqueous solutions, suggesting that it is this benzo[c]pyran derivative which interacts with the enzyme, rather than the quinone methide form.

GC–MS and FTIR evaluation of the six benzoyl-substituted-1-pentylindoles: Isomeric synthetic cannabinoids

This report compares the GC-MS and FTIR properties of all 6 regioisomeric benzoyl substituted-1-n-pentylindoles. These compounds have the benzoyl-group attached at each of the possible ring substituent positions of the indole ring. The six compounds have the same elemental composition C20H21NO yielding identical nominal and exact masses. Additionally, the substituents attached to the indole ring, benzoyl- and 1-n-pentyl-groups, are identical for all six isomers. The electron ionization mass spectra show equivalent regioisomeric major fragments resulting from cleavage of the groups attached to the central indole nucleus. Fragment ions occur at m/z 77 and 105 for the phenyl and benzoyl cations common to all six regioisomeric substances. Fragmentation of the benzoyl and/or pentyl groups yields the cations at m/z 234, 220, 214, 186 and 144. While the relative abundance of the ions varies among the six regioisomeric substances the 1-n-pentyl-3-benzoylindole and 1-n-pentyl-5-benzoylindole share very similar relative abundances for the major fragment ions. Chromatographic separations on a capillary column containing a 0.5μm film of 100% trifluoropropyl methyl polysiloxane (Rtx-200) provided excellent resolution of these six compounds. The elution order appears related to the relative distance between the two indole substituted groups. The latest eluting compounds (highest retention time) have the two substituents on opposite sides of the indole nucleus. Infrared absorption spectral data show the carbonyl absorption band for each of the benzoylindoles and provide distinguishing and characteristic information to individualize each of the regioisomers in this set of compounds.

Differentiation of methylenedioxybenzylpiperazines (MDBP) by GC-IRD and GC-MS

The substituted benzylpiperazine, 3,4-methylenedioxybenzylpiperazine (3,4-MDBP) and its regioisomer 2,3-methylenedioxybenzylpiperazine (2,3-MDBP) have almost identical mass spectra. Perfluoroacylation of the secondary amine nitrogen of these regioisomeric piperazines gave mass spectra with differences in relative abundance of some fragment ions. However the spectra did not yield any unique fragments for specific identification of one regioisomer to the exclusion of the other compound. Gas chromatographic separation coupled with infrared detection (GC-IRD) provides direct confirmatory data for structural differentiation between the two regioisomers. The mass spectrum in combination with the vapor-phase infrared spectrum provides for specific confirmation of each of the regioisomeric piperazines. The underivatized and perfluoroacyl derivative forms of the ring substituted benzylpiperazines were resolved on a 30-m capillary column containing an Rxi-50 stationary phase.

Analytical differentiation of 1-alkyl-3-acylindoles and 1-acyl-3-alkylindoles: isomeric synthetic cannabinoids.

The 1-alkyl-3-acylindoles and the inverse regioisomeric 1-acyl-3-alkylindoles can be prepared directly from a common set of precursor materials and using similar synthetic strategies. The EI mass spectra for these isomers show a number of unique ions which allow for the differentiation of the 1-alkyl-3-acylindole compounds from the inverse regioisomeric 1-acyl-3-alkylindoles. The base peak at m/z 214 in the 1-n-pentyl-3-benzoylindole represents the M-77 cation fragment resulting from the loss of the phenyl group, and this ion is not observed in the inverse isomer. The 1-benzoyl-3-n-pentylindole inverse regioisomer shows a base peak at m/z 105 for the benzoyl cation. Thus, these two base peaks are the result of fragmentation initiated at the carbonyl-oxygen for both isomers. The 1-pentyl-3-benzoylindole is characterized by the strong intensity carbonyl band at 1703 cm(-1), while the amide carbonyl appears as a strong band of equal intensity at 1681 cm(-1) in the 1-benzoyl-3-pentyl regioisomer.