Rapid Quantification of Tobramycin and Vancomycin by UPLC-TQD and Application to Osteomyelitis Patient Samples.

Rapid Quantification of Tobramycin and Vancomycin by UPLC-TQD and Application to Osteomyelitis Patient Samples.

J Chromatogr Sci. 2013 Jun 5;
Shou D, Dong Y, Shen L, Wu R, Zhang Y, Zhang C, Zhu Y

Tobramycin and vancomycin are the most commonly used antibiotics for the treatment of osteomyelitis. A sensitive and rapid method was developed for the analysis of tobramycin and vancomycin in human drainage tissue fluid. The procedure involved a simple liquid-liquid extraction of tobramycin, vancomycin and atenolol (internal standard) and separation by ultra-high performance liquid chromatography on an Acquity UPLC BEH C18 column (2.1 × 100 mm, 1.7 µm) with a mobile phase consisting of 0.1% (v/v) formic acid water solution and 0.1% (v/v) formic acid acetonitrile solution at a flow rate of 0.3 mL/min. Detection was performed by positive ion electrospray ionization in multiple reaction monitoring mode (m/z 468 ? 163 transitions for tobramycin; m/z 725 ? 144 for vancomycin; m/z 267 ? 74 for the internal standard). The retention times of tobramycin, vancomycin, and the internal standard were 0.68, 3.62 and 3.03 min, respectively. The total analysis time was less than 10 min. Excellent linear relationships (correlation coefficient > 0.99) were demonstrated between the area under the peak ratios of tobramycin and vancomycin to the internal standard in the drainage tissue fluid, and the concentration ranges were 1.25-100.00 mg/L and 0.50-150.00 mg/L for tobramycin and vancomycin, respectively. The intra-day and inter-day accuracy and precision (coefficient of variation) acceptance criteria for each quality control was ? 7.8% and the mean accuracy values were < 5.0% for tobramycin and < 4.0% for vancomycin. All experiments suggested the high-throughput potential of the proposed method. The method was successfully applied to investigate local delivery of tobramycin and vancomycin in four calcaneal osteomyelitis patients who had accepted drug-loaded artificial bone implantation. HubMed – drug

Riluzole: Validation of Stability-Indicating HPLC, D1 and DD1 Spectrophotometric Assays.

J Chromatogr Sci. 2013 Jun 5;
Saleh OA, El-Azzouny AA, Aboul-Enein HY, Badawey AM

A stability-indicating reversed-phase high-performance liquid chromatographic assay procedure has been developed and validated for riluzole in the presence of alkaline and oxidative degradation products. The liquid chromatographic separation was achieved and compared isocratically on C18 Zorbax ODS and Poroshell 120 EC-C18 columns by using a mobile phase containing methanol-water, pH = 3.10 (70:30, v/v), at a flow rate of 1 mL/min and ultraviolet detection at 264 nm. The method was linear over the concentration ranges of 20-200 µg/mL (r = 0.9997) and 10-200 µg/mL (r = 0.9995). The limit of detection and quantitation for the two columns were 2 and 6 µg/mL and 1 and 3 µg/mL, respectively.Moreover, spectrophotometric methods were applied for the determination of riluzole in the presence of its oxidative degradation products by using first derivative spectrophotometry at 252.5 and 275.0 nm. The method was linear over the concentration range of 1-20 µg/mL (r = 0.9995 and 0.9996) at the studied wavelengths, with limits of detection and quantitation of 0.1 and 0.3 µg/mL. In addition, the first derivative ratio spectrophotometry (DD1) method was applied for the determination of riluzole in the presence of its alkaline degradation product at 252.0, 278.5 and 306.3 nm by using 100 µg/mL of alkaline degraded riluzole as a divisor; riluzole was additionally determined in the presence of its hydrogen peroxide oxidative degradation products at 252.5, 275.0 and 305.0 nm by using 200 µg/mL of oxidative degraded riluzole as a divisor. The DD1 method was linear over the concentration range of 1-20 µg/mL (r = 0.9996, 0.9995 and 0.9996 for the alkaline degradation product at the three studied wavelengths, respectively; and r = 0.9995, 0.9996 and 0.9995 for the oxidative degradation product at the three studied wavelengths, respectively), with limits of detection and quantitation of 0.1 and 0.3 µg/mL for both alkaline and oxidative degradation products. The two studied chromatographic and spectrophotometric methods were comparable and display the required accuracy, selectivity, sensitivity and precision to assay riluzole in bulk and pharmaceutical dosage forms. Degradation products resulting from the stress studies did not interfere with the detection of riluzole, which indicates that these are stability-indicating assays. HubMed – drug

Baseline dependency of nicotine’s sensory gating actions: similarities and differences in low, medium and high P50 suppressors.

J Psychopharmacol. 2013 Jun 6;
Knott V, de la Salle S, Smith D, Phillipe T, Dort H, Choueiry J, Impey D

Reduced suppression of the P50 auditory event-related potential in schizophrenia patients relative to normal controls is indicative of a sensory gating deficit and is one of the most robust findings reported for functional brain abnormalities in this disorder. However, there is considerable gating variability in patients and controls and there is little understanding as to how inter-individual differences moderate gating responses to drugs and nicotinic agonists in particular, which have shown potential to reverse gating deficits. In this study the effects of acutely administered nicotine (gum, 6 mg) on sensory gating in a paired (S1-S2) auditory stimulus paradigm were investigated in 57 healthy, non-smoking volunteers stratified as low (n = 19), medium (n = 19) and high (n = 19) P50 suppressors on the basis of three separate baseline derived gating indices, P50 ratios, P50 difference scores, and gating difference waveforms. Relative to placebo, nicotine consistently improved gating in low suppressors as stratified with all three gating indices, exerted no effects in medium suppressors and reduced gating in high suppressors. Analysis of individual stimulus (S1, S2) amplitudes showed distinctly different mechanisms of action underlying nicotine effects in individuals with low and high baseline suppression. The results parallel similar findings of baseline-dependency in the gating effects of several antipsychotic drugs in healthy volunteers and support the use of group segmentation as a translational model in novel cognitive drug development for schizophrenia. HubMed – drug

Primary human non-small cell lung and pancreatic tumorgraft models-utility and applications in drug discovery and tumor biology.

Curr Protoc Pharmacol. 2013 Jun; Chapter 14: Unit14.26
Calles A, Rubio-Viqueira B, Hidalgo M

The number of therapeutic options for lung and pancreatic cancer is increasing because of the identification of new druggable molecular targets and development of new drug combinations. Reproducible, biologically relevant in vivo pre-clinical models are critical for this effort. The generation of patient-derived tumor xenografts has proven useful for integrating drug screening with biomarker discovery, discovering fundamental information in tumor biology, prioritizing drugs for clinical investigation, and personalizing treatments for these tumors. The protocol described in this unit details how to establish a direct in vivo subcutaneous primary tumorgraft and maintenance passages. The predictive value of a tumorgraft platform to guide personalized medicine is illustrated with the case of a patient with refractory advanced non-small cell lung cancer (NSCLC). The outcome of a patient for whom their own pancreatic tumorgraft revealed a remarkable sensitivity to mitomycin C based on a PALB2 mutation is also detailed. Curr. Protoc. Pharmacol. 61:14.26.1-14.26.21 © 2013 by John Wiley & Sons, Inc. HubMed – drug