Determination of MK-0767 enantiomers in human plasma by normal phase LC–MS/MS

Stabilization of Clinical Samples Collected for Quantitative Bioanalysis – A Reflection from The European Bioanalysis Forum

“…Therefore, the quantitative determination of both forms is important and ex vivo conversion should be prevented. Several factors play a role in racemization and epimerization such as pH (oxazepam), light (SU5416), temperature (MK-0767), enzyme activity (retinoic acid), or the presence of thiol groups (retinoic acid) [44][45][46][47]. Stabilizing strategies are, therefore, similar to those mentioned previously.…”

Separation and quantification of two diastereomers of a Drug Candidate in rat plasma by ultra-high pressure liquid chromatography/mass spectrometry

“…Therefore, minimizing ex vivo inter-conversion of these two diastereomers during sample processing was one of our main goals. Based on our previous experience, and scientific literature with enantiomeric inter-conversion [17,18], we adapted the sample preparation procedure to utilize an ice-water bath, whenever possible. There are three basic plasma sample cleanup procedures: protein precipitation, solid phase extraction (SPE) and liquid-liquid extraction (LLE) to achieve a rugged assay for biological samples.…”

“…The values for the R, S,-(A)/R, R-(A) concentration ratio plotted in the figure were determined by quantifying the concentration of each diastere- omer in plasma obtained after incubating R, S,-(A) with fresh EDTA-treated pooled rat blood. Based on previous work on chiral compound inter-conversion [17,18], an excessive amount of organic solvent may affect the epimerization of a compound, possibly by minimizing the differential effect of plasma protein binding of the individual diastereomers. Therefore, in this study, the total content of acetonitrile was kept at 0.5% (v/v) when spiking the drug into fresh blood.…”

“…Since chiral compounds can have distinct pharmacokinetic, pharmacological and toxicological properties, they must be characterized individually if racemates are administered or if inter-conversion of stereoisomers is possible [15][16][17][18]. In order to address stereo-chemical concerns for developing new drugs under current FDA guidelines [19], a rapid and sensitive assay for Drug A was required to quantify the two diastereomers for in vitro and in vivo studies.…”

Rapid and sensitive determination of fentanyl in dog plasma by on-line solid-phase extraction integrated with a hydrophilic column coupled to tandem mass spectrometry

“…Fortunately, the recent reported normal-phase high-performance liquid chromatography (HPLC) with silica-based columns and aqueous organic mobile phases becomes one of alternative method that can be applied to analyze polar compounds. There were many reports described the current advances in applying the silica columns with aqueous-polar organic mobile phases to improve LC conditions for the analysis of the polar compounds in biological fluids by LC/MS/MS [19][20][21]. Shou et al proposed by using a hydrophilic interaction chromatography (HILIC) as the analytical separation mode following on-line extraction with a hydrophobic extraction column coupled to LC/MS/MS to illustrate good peak shapes of chromatographs and better sensitivity than using the traditional reversed-phase C 18 column [22].…”