Identification of Drug Targets in Helicobacter pylori by in silico Analysis: Possible Therapeutic Implications for Gastric cancer.

Helicobacter pylori colonize stomach, inducing gastritis, ulcers and gastric cancer. Drugs are used to relieve pain, but not H. pylori infections. Hence, there is a need for discovery of drug targets and drugs for H. pylori. An objective of this current study is to identify drug targets for H. pylori. RAST was used to compare genomes of 23 H. pylori strains with Homo sapiens sapiens, other Helicobacter species (H. acinonychis, H. hepaticus, H. mustalae) and among them, to identify 13471 unique genes. Bacterial genes which are non-homologous to humans and essential for pathogen are identified using BLASTp. Later, 29 potential drug targets were identified by subjecting these genes to property analysis. Eleven of the 29 drug targets are already experimentally validated, lending credence to our approach. These methods have enabled rapid identification of drug targets with possible therapeutic implications for gastric cancer.

Precolumn o-phthalaldehyde-N-acetyl-L-cysteine derivatization followed by RP-HPLC separation and fluorescence detection of sitagliptin enantiomers in rat plasma.

An indirect reversed-phase high-performance liquid chromatographic separation and fluorescence detection of sitagliptin enantiomers in rat plasma was developed and validated. Deproteinized rat plasma containing racemic sitagliptin was derivatized with o-phthalaldehyde and N-acetyl-L-cysteine under alkaline conditions, converted to diastereomers, and separated on a Lichrospher 100 RP-18e column using 20 mM phosphate buffer and methanol (45:55 v/v) as a mobile phase under isocratic mode of elution at a flow rate of 1.0 mL/min. Fluorescence detection was performed at 330 and 450 nm as excitation and emission wavelengths, respectively. The method was linear in the range of 50-5000 ng/ mL for both enantiomers. The intra- and interday accuracy and precision were within the predefined limits of ≤15% at all concentrations. The method was successfully applied to a pharmacokinetic study of sitagliptin after 5 mg/kg oral administration to Wistar rats. Robustness of the method was evaluated using design of experiments.

An overview of the recent trends in development of HPLC methods for determination of impurities in drugs.

An extensive survey of the literature published in various analytical and pharmaceutical chemistry related journals has been conducted and the high-performance liquid chromatography (HPLC) methods which were developed and used for determination of process-related impurities in drugs have been reviewed. This review covers the time period from 1995 to 2001 during which around 450 analytical methods including all types of chromatographic and hyphenated techniques were reported. HPLC with UV detection was found to be the technique of choice for many workers and more than 200 methods were developed using LC-UV alone. A critical analysis of the reported data has been carried out and the present state-of-art of HPLC for determination of impurities of analgesic, antibiotic, anti-viral, anti-hypertensive, anti-depressant, gastro-intestinal and anti-neoplastic agents has been discussed.