Acetonitrile adduct formation as a sensitive means for simple alcohol detection by LC-MS.

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.

Evaluation of the General Solution Compatibility of Polymer Materials Used in Medical Devices such as Syringes.

The general compatibility between various polymers (plastic and elastomeric materials) commonly used in medical devices (e.g., syringes) and common solution-based pharmaceutical products was examined. Processes affecting material/solution compatibility that were considered included drug binding and material leaching. Considering binding, material/water equilibrium binding constants (E(b)) were determined for 14 organic solutes and the test materials. Correlations between the measured binding constants and the organic solute's octanol/water and hexane/water partition coefficients were obtained. In general, the elastomeric materials behaved similarly and interacted with acidic compounds differently than with neutral compounds. Alternatively, the plastic materials typically used in device components such as syringe barrels were relatively inert in the sense that they only minimally bound even the most lipophilc compounds. Considering leaching, both organic entities and trace elements/metals were extracted from the elastomers over the extraction pH range investigated. The plastic materials generally had lesser quantities of organic leachables than did the elastomers and contained little, if any, extractable trace elements/metals. LAY ABSTRACT: Polymeric materials are commonly used in medical devices such as syringes. The plastic materials may interact with drug products contained within the device, potentially affecting the quality of the drug products. These interactions may include leaching, which is the migration of entities out of the material and into the drug product, and binding, which is the migration of substances out of the drug product and into the material. This paper examines the magnitude of leaching and binding for several materials that can be used in syringe parts such as the syringe barrel, plunger, and tip cap.

Strategy for assessing the leachables impact of a material change made in a container/closure system.

Container/closure systems are extensively characterized in terms of their propensity to contribute leachable substances to the drug products they contain. Such a characterization is relevant until a change occurs in the composition or production of the container/closure system itself or the raw materials it is comprised of. When such a change occurs, it is necessary to ascertain the impact that the change would have on the validity and applicability of the previously performed leachables assessment. A general methodology for performing change control evaluations is developed in this manuscript and is illustrated via the use of a case study.