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De Vrieze M.,Ghent University | Lynen F.,Ghent University | Chen K.,Ghent University | Szucs R.,Pfizer | And 2 more authors.
Analytical and Bioanalytical Chemistry

Several in vitro methods have been tested for their ability to predict drug penetration across the blood-brain barrier (BBB) into the central nervous system (CNS). In this article, the performance of a variety of micellar liquid chromatographic (MLC) methods and immobilized artificial membrane (IAM) liquid chromatographic approaches were compared for a set of 45 solutes. MLC measurements were performed on a C18 column with sodium dodecyl sulfate (SDS), polyoxyethylene (23) lauryl ether (Brij35), or sodium deoxycholate (SDC) as surfactant in the micellar mobile phase. IAM liquid chromatography measurements were performed with Dulbecco's phosphate-buffered saline (DPBS) and methanol as organic modifier in the mobile phase. The corresponding retention and computed descriptor data for each solute were used for construction of models to predict transport across the blood-brain barrier (log BB). All data were correlated with experimental log BB values and the relative performance of the models was studied. SDS-based models proved most suitable for prediction of log BB values, followed closely by a simplified IAM method, in which it could be observed that extrapolation of retention data to 0 % modifier in the mobile phase was unnecessary. © 2013 Springer-Verlag Berlin Heidelberg. Source

Gansbeke W.V.,Ghent University | Polet M.,Ghent University | Hooghe F.,Ghent University | Devos C.,Research Institute for Chromatography RIC | Eenoo P.V.,Ghent University
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences

In 2013, the World Anti-Doping Agency (WADA) drastically lowered the minimum required performance levels (MRPLs) of most doping substances, demanding a substantial increase in sensitivity of the existing methods. For a number of compounds, conventional electron impact ionization gas chromatography tandem mass spectrometry (GC-EI-MS/MS) is often no longer sufficient to reach these MRPLs and new strategies are required. In this study, the capabilities of positive ion chemical ionization (PICI) GC-MS/MS are investigated for a wide range of drug related compounds of various classes by injection of silylated reference standards. Ammonia as PICI reagent gas had superior characteristics for GC-MS/MS purposes than methane. Compared to GC-EI-MS/MS, PICI (with ammonia as reagent gas) provided more selective ion transitions and consequently, increased sensitivity by an average factor of 50. The maximum increase (by factor of 500-1000) was observed in the analysis of stimulants, namely chlorprenaline, furfenorex and phentermine. In total, improved sensitivity was obtained for 113 out of 120 compounds. A new GC-PICI-MS/MS method has been developed and evaluated for the detection of a wide variety of exogenous doping substances and the quantification of endogenous steroids in urine in compliance with the required MRPLs established by WADA in 2013. The method consists of a hydrolysis and extraction step, followed by derivatization and subsequent 1μL pulsed splitless injection on GC-PICI-MS/MS (16min run). The increased sensitivity allows the set up of a balanced screening method that meets the requirements for both quantitative and qualitative compounds: sufficient capacity and resolution in combination with high sensitivity and short analysis time. This resulted in calibration curves with a wide linear range (e.g., 48-9600ng/mL for androsterone and etiochanolone; all r20.99) without compromising the requirements for the qualitative compounds. © 2015 Elsevier B.V. Source

Ochiai N.,GERSTEL K.K. | Sasamoto K.,GERSTEL K.K. | Ieda T.,GERSTEL K.K. | David F.,Research Institute for Chromatography RIC | Sandra P.,Research Institute for Chromatography RIC
Journal of Chromatography A

As reproducible coating of stir bars with more polar phases was found to be very difficult, a supporting grid was used in the development of an ethyleneglycol-modified Silicone (EG Silicone) coated stir bar. This new polar coating showed good performance for the extraction of polar solutes, but long term use also showed degradation of the coating due to friction while stirring. In order to address the lower robustness of the EG Silicone stir bar which has a much softer coating compared to a conventional polydimethylsiloxane (PDMS) stir bar, a novel SBSE procedure termed multi-SBSE (mSBSE) was developed. mSBSE consists of the robust PDMS stir bar stirring at the bottom of the vial and the EG Silicone stir bar attached on the inner side wall of the vial (a magnetic clip is used for the set-up). After extraction, the two stir bars are placed in a single glass desorption liner and are simultaneously thermally desorbed. The desorbed compounds were analyzed by thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS). Compared to conventional SBSE, mSBSE provides more uniform enrichment of a wide range of odor compounds in aqueous sample since both stir bars can complement each other, while eliminating the damage of the EG Silicone phase during the extraction. The robustness of the EG Silicone stir bar was dramatically increased and more than 30 extraction and desorption cycles were possible without loss in performance. The recoveries for polar solutes such as 2-acetyl pyrrole (logKow: 0.55), benzyl alcohol (logKow: 1.08), guaiacol (logKow: 1.34), and indole (logKow: 2.05) were increased by a factor of about 2-7. The mSBSE-TD-GC-MS method showed good linearity (r2>0.9913) and high sensitivity (limit of detection: 0.011-0.071ngmL-1) for the test compounds spiked in water. The feasibility and benefit of the method was demonstrated with analysis of odor compounds in roasted green tea. The normalized areas obtained from mSBSE showed the best enrichment for most of the selected compounds compared to conventional SBSE using the PDMS stir bar or the EG Silicone stir bar. Fifteen compounds were determined in the range of 0.15-210ngmL-1 (RSD<14%, n=6). © 2013 Elsevier B.V. Source

Pauwels N.,Ghent University | Aspeslagh S.,Ghent University | Vanhoenacker G.,Research Institute for Chromatography RIC | Sandra K.,Research Institute for Chromatography RIC | And 5 more authors.
Organic and Biomolecular Chemistry

A synthetic approach is presented for the synthesis of galacturonic acid and d-fucosyl modified KRN7000. The approach allows for late-stage functionalisation of both the sugar 6′′-OH and the sphingosine amino groups, which enables convenient synthesis of promising 6′′- modified KRN7000 analogues. © The Royal Society of Chemistry 2011. Source

Sandra K.,Research Institute for Chromatography RIC | Vandenheede I.,Research Institute for Chromatography RIC | Sandra P.,Research Institute for Chromatography RIC
Journal of Chromatography A

Protein biopharmaceuticals such as monoclonal antibodies and therapeutic proteins are currently in widespread use for the treatment of various life-threatening diseases including cancer, autoimmune disorders, diabetes and anemia. The complexity of protein therapeutics is far exceeding that of small molecule drugs; hence, unraveling this complexity represents an analytical challenge. The current review provides the reader with state-of-the-art chromatographic and mass spectrometric tools available to dissect primary and higher order structures, post-translational modifications, purity and impurity profiles and pharmacokinetic properties of protein therapeutics. © 2013 Elsevier B.V. Source

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