Purification of pharmaceutical preparations using thin-layer chromatography to obtain mass spectra with Direct Analysis in Real Time and accurate mass spectrometry.

Forensic analysis of pharmaceutical preparations requires a comparative analysis with a standard of the suspected drug in order to identify the active ingredient. Purchasing analytical standards can be expensive or unattainable from the drug manufacturers. Direct Analysis in Real Time (DART™) is a novel, ambient ionization technique, typically coupled with a JEOL AccuTOF™ (accurate mass) mass spectrometer. While a fast and easy technique to perform, a drawback of using DART™ is the lack of component separation of mixtures prior to ionization. Various in-house pharmaceutical preparations were purified using thin-layer chromatography (TLC) and mass spectra were subsequently obtained using the AccuTOF™- DART™ technique. Utilizing TLC prior to sample introduction provides a simple, low-cost solution to acquiring mass spectra of the purified preparation. Each spectrum was compared against an in-house molecular formula list to confirm the accurate mass elemental compositions. Spectra of purified ingredients of known pharmaceuticals were added to an in-house library for use as comparators for casework samples. Resolving isomers from one another can be accomplished using collision-induced dissociation after ionization. Challenges arose when the pharmaceutical preparation required an optimized TLC solvent to achieve proper separation and purity of the standard. Purified spectra were obtained for 91 preparations and included in an in-house drug standard library. Primary standards would only need to be purchased when pharmaceutical preparations not previously encountered are submitted for comparative analysis. TLC prior to DART™ analysis demonstrates a time efficient and cost saving technique for the forensic drug analysis community. Copyright © 2011 John Wiley & Sons, Ltd.

The use of molecularly imprinted sol-gels in pharmaceutical separations.

This paper illustrates the potential of the sol-gel process to imprint the pharmaceutical active--N-[N-[(1S)-1-carboxssy-3-phenylpropyl]-l-lysyl]-L-proline, (lisinopril dihydrate). This template exhibits unique difficulties such as limited solubility in non-polar and most polar porogens with multiple functionality evident in its 4 pKa values. Selectivity for this template was achieved using a 3-monomer sol-gel system utilising solid phase extraction (SPE). Analysis of the template and its related substances was achieved using HPLC. The effect of solvent polarity on the rebinding of the template was studied. Through optimisation of porogen and extraction solvent, the imprinted material (MIP) demonstrated enhanced selectivity, for the template, over a non-imprinted material (NIP). Selectivity was also illustrated for the original template over two of its related substances. The effect of starting monomer ratio on selectivity was studied to determine the interactions, which could best be exploited to further enhance selectivity.

Chemical and analytical characterization of related organic impurities in drugs.

A system is proposed for the classification of related organic impurities in drugs and drug products including among others (separated and non-separated) intermediates, various kinds of by-products, among them products of different side reactions, epimeric/diastereomeric, enantiomeric impurities, impurities in natural products, and finally degradation products. Examples are taken mainly from the author's own experience and from among the named impurities in the European Pharmacopoeia with focus on impurities in hydrocortisone, prednisolone, enalapril maleate, lisinopril, ethynodiol diacetate, pipecuronium bromide, cimetidine, and ethynylsteroids. The methodological aspects of impurity profiling from the detection to the identification/structure elucidation and quantitative determination of impurities are briefly summarized.

Reversed-phase liquid chromatography of lisinopril conformers.

The effect of flow rate, temperature, pH, organic solvent and counter ion on peak shape and separation of the cis and trans conformers of lisinopril are investigated by HPLC. It was demonstrated that complete separation of the two isomers can be achieved at low temperature at either neutral or low pH together with appropriate type and concentration of organic solvent, whereas the elution of lisinopril as a single peak is favored by a decrease of flow rate, elevated temperature, choice of organic solvent (type and amount) and the use of an appropriate counter ion concentration.