The utility of sulfonate salts in drug development.

The issue of controlling genotoxic impurities in novel active pharmaceutical ingredients (APIs) is a significant challenge. Much of the current regulatory concern, has been focused on the formation and control of genotoxic sulfonate esters. This is linked with the withdrawal of Viracept (Nefinavir mesilate) from European markets in mid-2007, over concerns about elevated levels of ethyl methanesulfonate (EMS).

Development and validation of an automated static headspace gas chromatography-mass spectrometry (SHS-GC-MS) method for monitoring the formation of ethyl methane sulfonate from ethanol and methane sulfonic acid.

An automated sample preparation and analysis procedure was developed to monitor the formation of ethyl methane sulfonate from reaction mixtures containing ethanol and methane sulfonic acid. The system is based on a liquid handling robot combined with a static headspace module. The formed ethyl methane sulfonate is analysed after derivatisation with pentafluorothiophenol using static headspace-gas chromatography-mass spectrometry (SHS-GC-MS).

PQRI recommendations on particle-size analysis of drug substances used in oral dosage forms.

This document provides information for the Pharmaceutical Industry and the Federal Drug Administration (FDA) regarding the selection of suitable particle-size analysis techniques, development and validation of particle-size methods, and the establishment of acceptance criteria for the particle size of drug substances used in oral solid-dosage forms. The document is intended for analysts knowledgeable in the techniques necessary to conduct particle-size characterization (a table of acronyms is provided at the end of the document). It is acknowledged that each drug substance, formulation, and manufacturing process is unique and that multiple techniques and instruments are available to the analyst.

Determination of isepamicin sulfate and related compounds by high performance liquid chromatography using evaporative light scattering detection.

A simple reversed phase high performance liquid chromatographic method was developed for the analysis of isepamicin sulfate. The use of evaporative light scattering detection eliminates the need for sample derivatization. Separation of the isepamicin aminoglycoside from structurally similar related compounds was achieved using two Waters X-Terra RP18 columns connected in tandem at 10 degrees C.

Determination of enantiomers in a synthetic argininal peptide using capillary zone electrophoresis and high-performance liquid chromatography.

SCH 201781 is a synthetic argininal peptide containing two chiral centers and an aromatic sulfonamide group. It can exist as four reversible forms, the aldehyde, the hydrate, and two diastereomeric aminals. Capillary zone electrophoresis (CZE) and reversed-phase high-performance liquid chromatographic (HPLC) methods were developed to separate and quantitate the enantiomers in SCH 201781.