Development of a hydrophilic interaction high-performance liquid chromatography method for the determination of glycine in formulations of therapeutic immunoglobulins.

In the study presented, a simple analytical method for the direct determination of glycine in immunoglobulins by hydrophilic interaction liquid chromatography was developed. The HPLC separation was performed using a SeQuant ZIC-HILIC column (250 mm × 4.6 mm i.d, 5 µm) with the isocratic mobile phase consisting of ammonium formate (20 mM) and acetonitrile (30:70, v/v), and the flow rate set at 0.8 mL/min. UV detection was carried out at a wavelength of 210 nm. The procedure was validated for specificity, precision, linearity, accuracy, limit of detection, limit of quantitation, and robustness. The calibration curve was found to be linear within the concentration range of 1.2-3.6 mg/mL. RSD values for intra-day and inter-day precision were in the range of 0.66 to 1.84%. The limit of quantification and limit of detection were 0.10 mg/mL and 0.03 mg/mL, respectively. The developed chromatographic method was applied for the glycine analysis in various immunoglobulins.

Tyrenes: synthesis of new antiproliferative compounds with an extended conjugation.

A series of substituted styryl-acrylonitriles was designed and synthesized. The new compounds, called tyrenes, were tested for the ability to inhibit acute lymphocytic leukemia (ALL) cancer cell growth, as well as on their toxicity to normal bone marrow (NBM) cells. The results showed that 3,4-dihydroxystyryl-acrylonitriles, in particular CR-4, revealed great potency as antitumor agents, and also exhibited low toxicity to normal cells. The effectiveness of these compounds with extended conjugation may be due to their possible functioning as reactive Michael acceptors.

Inhibition of acute lymphoblastic and myeloid leukemias by a novel kinase inhibitor.

In recent years, synthetic tyrosine kinase inhibitors have made a rapid transition from basic research to therapeutic application. These compounds represent a major clinical advance in the approach to cancer in their relative specificity of action and decreased toxicity. We report here the effects of a novel tyrosine kinase inhibitor CR4 that interferes with growth-promoting pathways to markedly inhibit the growth and survival of both Philadelphia-positive and -negative acute lymphoblastic leukemia (ALL) as well as acute myeloid leukemia (AML). While efficiently ablating leukemic cell growth, normal cell growth and differentiation remain unaffected by CR4. CR4 demonstrates an ability to inhibit the function of multiple growth-critical kinases and yet exhibits a low level of cytotoxicity. These findings suggest that CR4 may prove to be highly effective as a therapeutic agent.