Anthony Rees

Fast identification of selective resins for removal of genotoxic aminopyridine impurities via screening of molecularly imprinted polymer libraries

This study describes the identification and evaluation of molecularly imprinted polymers (MIPs) for the selective removal of potentially genotoxic aminopyridine impurities from pharmaceuticals. Screening experiments were performed using existing MIP resin libraries to identify resins selective towards those impurities in the presence of model pharmaceutical compounds. A hit resin with a considerable imprinting effect was found in the screening and upon further investigation, the resin was found to show a broad selectivity towards five different aminopyridines in the presence of the two model active pharmaceutical ingredients (APIs) piroxicam and tenoxicam.

Direct aqueous supercritical fluid extraction coupled on-line with liquid chromatography-tandem mass spectrometry for the analysis of polyether ionophore antibiotics in water.

A direct aqueous SFE system designed to extract water samples contained in vials has been coupled on-line with a reverse phase LC-MS-MS system using a single 10-port valve. An SFE trap system using C(1) stationary phase connected to a C(18) analytical HPLC column enabled the SFE-LC-MS-MS analysis of three polyether ionophore antibiotics in water using a step gradient. A quantitative SFE-LC-MS-MS method has been developed whereby the progress of SFE can be monitored directly on-line such that ionophore recovery profile data from a single water sample can be obtained. Using a continuous direct aqueous SFE period of 75 min, the SFE-LC-MS-MS recoveries of the ionophores were: monensin 76.2% with RSD 4.1%, lasalocid 84.6% with RSD 3.8% and narasin 91.2% with RSD 3.2%. With positive ion electrospray ionization, the SFE-LC-MS-MS system using a 4 mL water sample provided multiple reaction monitoring (MRM) limits of detection for monensin and lasalocid each equivalent to 90 ng/L whereas 30 ng/L for narasin. A two-way valve controlling carbon dioxide distribution to the SFE vessel has provided a means for the initial investigation of the recovery of ionophore sodium salts from water using static SFE.

Drugs in water: Analysis at the part-per-billion level using direct supercritical fluid extraction of aqueous samples coupled on-line with ultraviolet-visible diode-array liquid chromatography-mass spectrometry

A high pressure ten port switching valve has provided a means of interfacing a direct aqueous SFE vessel to an LC–MS instrument equipped with a UV/VIS diode-array detector. Analyte trapping and analysis were performed using a coupled octadecylsilane (ODS)–amino column system. Using full scan ammonia chemical ionization, the combined SFE–LC–MS instrumentation enabled the analysis of estrone, hexestrol and zeranol in water each at the 200 ppb level.

Analysis of Phenols in Water at the ppb Level Using Direct Supercritical Fluid Extraction of Aqueous Samples Combined On-line With Supercritical Fluid Chromatography–Mass Spectrometry

A high pressure multivalve switching system has provided a means of interfacing a direct aqueous SFE vessel to a packed column SFC-MS system. Using full scan negative ion atmospheric pressure chemical ionization, the combined SFE–SFC–MS instrumentation enabled the analysis of phenols in water at the 40 ppb level.

Dynamic aqueous supercritical fluid extraction of the enzymic hydrolysis of testosterone-β-D-glucuronide. Analysis of liberated testosterone by gas chromatography–mass spectrometry

The enzymic hydrolysis of testosterone-β-D-glucuronide has been performed under aqueous SFE conditions. Liberated testosterone was continuously extracted and trapped onto an ODS HPLC column. Results of quantitative GC–MS indicate that 70.1% of testosterone-β-D-glucuronide was hydrolysed after 135 min of enzymic digestion resulting in 88% of the free testosterone being trapped after 120 min of dynamic aqueous SFE.

Supercritical fluid extraction coupled on-line with mass spectrometry and spectroscopic techniques

Previous chapters have described the on-line coupling of supercritical fluid extraction (SFE) with a variety of chromatographic techniques, including: gas chromatography (GC), capillary supercritical fluid chromatography (cSFC), packed column supercritical fluid chromatography (SFC) and high-performance liquid chromatography (HPLC). Three major advantages of coupling SFE with chromatography are that: all of the extracted analytes can be transferred (if required) to the chromatographic system, this being particularly valuable in the case of ultra-tracelevel studies provided robust on-line SFE procedures can be developed, considerable savings in analyses times can be achieved potential errors associated with off-line sample preparation manipulations can be eliminated.