Ultra-fast LC-MS/MS in therapeutic drug monitoring: Quantification of clozapine and norclozapine in human plasma.

A novel approach to high-throughput, targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis has been developed. A single chromatographic system can be used for the analysis of a range of 20 drugs and metabolites with a total analysis time of 36 s (one 96-well plate of prepared samples per hour). To demonstrate the applicability of this approach to quantitative analysis, a method has been validated for the therapeutic drug monitoring of clozapine and norclozapine following automated extraction from human plasma.

Performance of charged aerosol detection with hydrophilic interaction chromatography.

The performance of the charged aerosol detector (CAD) was investigated using a diverse set of 29 solutes, including acids, bases and neutrals, over a range of mobile phase compositions, particularly with regard to its suitability for use in hydrophilic interaction chromatography (HILIC). Flow injection analysis was employed as a rapid method to study detector performance. CAD response was 'quasi-universal', strong signals were observed for compounds that have low volatility at typical operating (room) temperature.

Comparison of peak shape in hydrophilic interaction chromatography using acidic salt buffers and simple acid solutions.

The retention and peak shape of neutral, basic and acidic solutes was studied on hydrophilic interaction chromatography (HILIC) stationary phases that showed both strong and weak ionic retention characteristics, using aqueous-acetonitrile mobile phases containing either formic acid (FA), ammonium formate (AF) or phosphoric acid (PA). The effect of organic solvent concentration on the results was also studied. Peak shape was good for neutrals under most mobile phase conditions.

Effect of increasing concentration of ammonium acetate as an additive in supercritical fluid chromatography using CO2-methanol mobile phase.

The effects of increasing concentrations of ammonium acetate additive in supercritical fluid chromatography were studied on silica, 2-ethyl-pyridine and endcapped 2-ethyl-pyridine stationary phases. The study involved the addition of increasing concentrations of the ammonium acetate either in the mobile phase modifier (methanol) or in the sample solvent. The effects of ammonium acetate on retention and peak shape of the analytes were evaluated.

Ionisation in the absence of high voltage using supercritical fluid chromatography: a possible route to increased signal.

Supercritical fluid chromatography (SFC) is fast becoming a technique of choice for the analysis of a wide range of compounds and has been found to be complementary to high-performance liquid chromatography (HPLC). The combination of SFC and mass spectrometry (MS) affords a very useful tool in the separation and analysis of compounds. In this study the ionisation of samples in the absence of an applied electrospray voltage has been observed when using SFC/MS, with some compounds showing increased sensitivity when all ionisation source high voltage (HV) is removed.

Prediction of retention for sulfonamides in supercritical fluid chromatography.

Properties-retention studies were undertaken on a test library of sulfonamides using supercritical fluid chromatography with CO(2)-MeOH mobile phases (in the presence or absence of additive) and a 2-ethyl-pyridyl column. Taking a restricted range of retention ratios, k (10.98).

Investigations into the Manzamine Alkaloid Biosynthetic Hypothesis.

The biomimetic synthesis of a pentacyclic alkaloid (keramaphidin B, 1), an intermediate in the biogenetic pathway to the manzamine alkaloids, has been achieved. Compound 1 was formed by an intramolecular Diels-Alder reaction of macrocycle 2 in buffer followed by reduction with NaBH . This reaction provides the first direct expeimental evidence for the authors' biosynthetic hypothesis.