Current Pharmaceutical Analysis - Volume 6, Issue 2, 2010

An increasing number of reported cases of drug resistant Staphylococcus aureus and Pseudomonas aeruginosa, demonstrate the urgent need for new therapeutics that are effective against such and other multi-drug resistant bacteria. Antimicrobial peptides have for two decades now been looked upon as interesting leads for development of new therapeutics combating these drug resistant microbes. High-throughput screening of peptide libraries have generated large amounts of information on peptide activities. However, scientists still struggle with explaining the specific peptide motifs resulting in antimicrobial activity. Consequently, the majority of peptides put into clinical trials have failed at some point, underlining the importance of a thorough peptide optimization. An important tool in peptide design and optimization is quantitative structure-activity relationship (QSAR) analysis, correlating chemical parameters with biological activities of the peptide, using statistical methods. In this review we will discuss two different in silico strategies of computer-aided antibacterial peptide design, a linear correlation model build as an extension of traditional principal component analysis (PCA) and a non-linear artificial neural network model. Studies on structurally diverse peptides, have concluded that the PCA derived model are able to guide the antibacterial peptide design in a meaningful way, however requiring rather a high homology between the peptides in the test-set and the in silico library, to ensure a successful prediction. In contrast, the neural network model, though significantly less explored in relation to antimicrobial peptide design, has proven extremely promising, demonstrating impressive prediction success and ranking of random peptide libraries correlating well with measured activities.

An advanced capillary electrophoresis (CE) based on the on-line combination of the CE with a sample preparation procedure (preconcentration, purification, analyte derivatization) is presented and supplemented by applications in the field of an ultratrace chiral determination of biologically active compounds. A brief description of theory, benefits and limitations is given for many applicable (i) electrophoretic techniques (stacking) and (ii) nonelectrophoretic techniques (chromatography, extraction, membrane filtration/dialysis, flow injection) implemented in conventional CE for the effective on-line sample preparation. Practical potentialities of such CE hyphenations are demonstrated on many application examples aimed mainly to biological matrices and monitored within the period of last decade in the present review paper. Perspectives for full automatization and miniaturization linked with this analytical strategy can offer new insight into biomedical analytical research/practice in near future. It should also be realized that while this review is limited to chiral separation, the techniques are generally applicable.

This paper provides an overview of the applications of crown ethers as buffer additive in capillary electrophoresis. The applications area can be categorized into the separation of inorganic cations; chiral separation and separation of organic compounds include positional isomers. The use of background electrolytes combining cyclodextrins and crown-ethers for both chiral and non-chiral separation is also presented. Applications published up to the year 2009 from each category are summarized.

The increasing demand for enantiopure drugs has led to the development of a variety of stereoselective separation technologies. Among them, high performance liquid chromatography (HPLC) is well recognized as a powerful, fast and efficient technique, which has been successfully employed for analysis and preparation of enantiomers of drugs. Nowadays, liquid chromatographic techniques are the focus of intensive research, which lead to the rational design and production of highly selective and efficient chromatographic materials. This review focuses on various HPLC methods and related hyphenated techniques (including LC-MS, LC-OR detector, LC-CD detector) for chiral separation of pharmaceuticals, many new developments and applications are introduced in chiral HPLC separations in recent years. In this paper, the usage of new materials as chiral stationary phases (CSPs) in liquid chromatography for enantiomeric discrimination is investigated in detail. Moreover, hyphenated techniques are very useful for chiral separation of HPLC, especially for separation of new pharmaceuticals.

The Raman scattering technique is a vibrational molecular spectroscopy, which derives from an inelastic light scattering process. In recent years, Raman spectroscopy is experiencing a surge in interest in solid-state pharmaceutical applications with increased use both in industry and academia. It is a rapid, non-destructive, non-invasive method which does not require sample preparation and measurements can be done in aqueous environments. It can be used for qualitative as well as quantitative analysis with the assistance of chemometrics. Current pharmaceutical applications cover a broad range from discovery to manufacturing of drugs in the pharmaceutical industry like identifying polymorphs, monitoring real-time processes, detection of counterfeit and adulterated pharmaceutical products and imaging solid dosage formulations. Raman imaging combines spectral and spatial information and generates chemical image of a twodimensional area of a sample. It shows promising results in its ability to visualize the drug and excipients distribution in pharmaceutical formulations such as tablets, creams and ointments. This article explores the above recent applications of Raman spectroscopy in the pharmaceutical field.

Stability testing is an essential part of pharmaceutical development program and is required by regulatory agencies for establishing and sustaining the high quality products. The ultimate purpose of stability testing is to understand how to design a drug product and its packaging such that the product has appropriate physical, chemical and microbiological properties during a defined shelf life when stored and used as labeled. This write up provides a review on brief information about role of stability testing in the different stages of drug product development as well as comparison and summarized form of stability testing guidelines for pharmaceutical products issued by International Conference on Harmonization and World Health Organization.