ABSTRACT
The objective of this work was to develop a HPLC-DAD method suitable for the screening of food contact materials for a total of 63 monomeric and polymeric photoinitiators and amine synergists. Such multi-analyte methods are worthwhile for official control laboratories, where normally no information about the composition of the applied inks or varnishes on the printed or lacquered materials is available and thus target analyses are not feasible. The polymeric analytes were each separated in a multitude of substance peaks, which largely overlaid those of the other compounds. Thus, for 13 polymeric photoinitiators and amine synergists a hydrolysis method was developed that reduced the number of ultraviolet (UV) detectable peaks to only one. This allowed easier identification and--preliminary--semi-quantification of these polymeric substances with adequate limits of detection. The remaining 50 photoinitiators and amine synergists were combined in one HPLC-DAD method. But since many of these substances are structurally related, partly retention times and spectra did not differ significantly. Thus selectivity was enhanced by preparing a database containing all spectra and retention times of the investigated compounds. Furthermore, the retention times of those 50 substances were calculated relative to two internal standards to overcome variances of retention from run to run or due to matrix effects. The developed method was tested for the analysis of food contact materials. Extractions of these were performed with acetonitrile and partially the extracts were subsequently concentrated in a steam of nitrogen. Limits of detection of photoinitiators and amine synergists in concentrated packaging extracts were in the range between 0.02 and 5.5 µg dm(-2).
Subject(s)
Food Contamination/analysis , Food Packaging , Hazard Analysis and Critical Control Points/methods , Amines/agonists , Chromatography, High Pressure Liquid/methods , Humans , Hydrolysis , Ink , Limit of Detection , Molecular Structure , Photosensitizing Agents/analysis , Photosensitizing Agents/chemistry , Polymers/analysis , Polymers/chemistry , Ultraviolet RaysABSTRACT
The use of cholinergic drugs, either alone or in combination with other drugs, has been suggested as an approach to improve treatment outcome for patients suffering from neuropathic pain. The present study was undertaken in the rat spared nerve injury model of neuropathic pain to evaluate the effect of the cholinesterase inhibitor donepezil when administered (1) alone and (2) as low-dose in combination with the first-line recommendation gabapentin. The co-administration studies were performed following single and multiple dosing. Single, parenteral dosing of donepezil (1, 1.5 and 3 mg/kg s.c.) produced a dose-dependent reversal of the neuropathic pain behaviour. Co-administration of a sub-effective dose of donepezil (0.5 mg/kg s.c.) and low doses of gabapentin (10 and 30 mg/kg s.c.) resulted in a three- to fourfold increase of the analgesic effect, in comparison with gabapentin administered alone. Following multiple, oral dosing, gabapentin (25 mg/kg p.o.) was administered once daily over 20 days. Addition of donepezil (1.5 mg/kg p.o.) from day 11 to day 20 resulted in improved analgesia during the period of combination therapy, in comparison with the gabapentin monotherapy period. Furthermore, the treatment effects were stable in both the mono- and the combination therapy period, indicating that tolerance development does not occur within the studied time frame. In conclusion, the results from this preclinical study support the use of donepezil as adjunctive to gabapentin to improve the therapeutic outcome in the management of neuropathic pain.
Subject(s)
Amines/agonists , Analgesics/agonists , Cholinesterase Inhibitors/pharmacology , Cyclohexanecarboxylic Acids/agonists , Indans/pharmacology , Neuralgia/drug therapy , Peripheral Nervous System Diseases/drug therapy , Piperidines/pharmacology , Animals , Cholinesterase Inhibitors/therapeutic use , Disease Models, Animal , Donepezil , Drug Administration Schedule , Drug Combinations , Drug Synergism , Gabapentin , Indans/therapeutic use , Male , Neuralgia/enzymology , Neuralgia/etiology , Peripheral Nervous System Diseases/complications , Peripheral Nervous System Diseases/enzymology , Piperidines/therapeutic use , Rats , Rats, Sprague-Dawley , gamma-Aminobutyric AcidABSTRACT
"Party pills" continue to be legally sold though the main ingredient is no longer 1-benzylpiperazine. Dimethylamylamine (DMAA) is a synthetic stimulant and is one of the main ingredients of new "BZP-free party pills". Though patented in the 1950s as a nasal decongestant, little is known of its pharmacology via the ingested route. This case report describes a 21-year-old male who suffered a cerebral haemorrhage shortly after ingesting two capsules of DMAA.
