Simple alcohols formed protonated acetonitrile adducts containing up to two acetonitrile molecules when analyzed by ESI or APCI in the presence of acetonitrile in the solvent. These acetonitrile adducts underwent dissociation to form a nitrilium ion, also referred to as the substitution ion. Diols and triols behaved differently. In ESI, they formed only one acetonitrile adduct containing one acetonitrile. The S ion was not observed in ESI and was only weakly observed from the dissociation of the (M + ACN + H)(+) ion. On the other hand, the S ion was abundantly formed from the diols in APCI. This formation of acetonitrile adducts and substitution ion from simple alcohols/diols offers an opportunity to detect simple alcohols/diols sensitively by LC-MS interfaced by ESI or APCI. The utility of this chemistry was demonstrated in a method developed for the quantification of cyclohexanol in rat plasma by monitoring the CID-induced fragmentation from the S ion to a fragment ion.
Current therapeutic treatment options for osteoarthritis entail significant safety concerns. A novel ropivacaine crystalline microsuspension for bolus intra-articular (IA) delivery was thus developed and studied in a peptidoglycan polysaccharide (PGPS)-induced ankle swelling rat model. Compared with celecoxib controls, both oral and IA, ropivacaine IA treatment resulted in a significant reduction of pain upon successive PGPS reactivation, as demonstrated in two different pain models, gait analysis and incapacitance testing. The reduction in pain was attended by a significant reduction in histological inflammation, which in turn was accompanied by significant reductions in the cytokines IL-18 and IL-1β. This may have been due to inhibition of substance P, which was also significantly reduced. Pharmacokinetic analysis indicated that the analgesic effects outlasted measurable ropivacaine levels in either blood or tissue. The results are discussed in the context of pharmacologic mechanisms both of local anesthetics as well as inflammatory arthritis.
Although ethanol/water mixtures are frequently used as simulating solvents in extractables studies, it is difficult to establish and justify what the right proportion of ethanol is for a particular drug product. A solvent strength model has been developed based on the leaching behavior of a model compound, di-(2-ethylhexyl) phthalate (DEHP), from a reference source material, plasticized poly-(vinyl chloride) (PVC). By measuring the level of DEHP leached into a drug product from the reference source material, one can use the model to calculate the correct ethanol proportion in the simulating solvent.Using this approach, ethanol/water proportions have been obtained for certain drug products. Additionally, the leaching profiles for DEHP obtained in this study were noted to be consistent with such profiles for other extractables from the PVC reference source material and with other investigations of ethanol/water as model stimulants.
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