Thimerosal Analysis in Ketorolac Tromethamine Ophthalmic Solution. Comparing Hplc and Colorimetric Techniques

Ketorolac tromethamine, a pyrrolopyrrole, is a nonsteroidal anti-inflammatory drug under development as a topical agent for treating ocular disorders associated with inflammation. Thimerosal is a commonly-used antimicrobial preservative in ophthalmic solutions. This report describes both stability-specific (HPLC) and non-specific (colorimetric) methodology for determining thimerosal stability in ketorolac ophthalmic solution.

The HPLC technique used a reverse-phase Whatman RAC II (C8) column (5 micron particle size. 10 cm × 4.6 mm 1.0.) with a 30:67:3 by volume mixture of methanol:10mM acetate buffer (pH 4.5) and tetrahydrofuran as the mobile phase. Detection was at 254 nm.

Thimerosal peak purity, in thermally stressed ketorolac ophthalmic solution 1s confirmed using absorbance ratio techniques. Accuracy and linearity data are presented.

In addition, a colorimetric (dithizone) technique for quantifying total organic mercury in solution is described. Both the HPLC and colorimetric techniques were used to evaluate thimerosol stability 1n ketorolac ophthalmic solution samples exposed to both thermal and photochemical stress. Results indicated that a stability specific HPLC technique does not reflect accurately the total mercury content 1n ophthalmic solution. Mercury, 1n other forms than thimerosal, may contribute to the antimicrobial efficacy of thimerosal 1n ophthalmic solutions.     

46,XY/46,XY,21q- mosaicism in an infant with neutropenia and properdin deficiency

An infant with neutropenia, properdin deficiency, and a 46,XY/46,XY,21q- mosaicism is described. It is not known whether these two findings are related to the missing 21q material. The propositus is normal in appearance, and has none of the phenotypic features associated with the G-group deletion syndromes.     

X-Ray Tomoscopy Reveals the Dynamics of Ice Templating

Little experimentally explored and understood are the complex dynamics of microstructure formation by ice-templating when aqueous solutions or slurries are directionally solidified (freeze cast) into cellular solids. With synchrotron-based, time-resolved X-ray tomoscopy it is possible to study in situ under well-defined conditions the anisotropic, partially faceted growth of ice crystals in aqueous systems. Obtaining one full tomogram per second for ≈270 s with a spatial resolution of 6 µm, it is possible to capture with minimal X-ray absorption, the freezing front in a 3% weight/volume (w/v) sucrose-in-water solution, which typically progresses at 5–30 µm s⁻¹ for applied cooling rates of $\dot{C}$ = 1–10 °C min⁻¹. These time and length scales render X-ray tomoscopy ideally suited to quantify in 3D ice crystal growth and templating phenomena that determine the performance-defining hierarchical architecture of freeze-cast materials: a complex pore morphology and “ridges”, “jellyfish cap”, and “tentacle”-like secondary features, which decorate the cell walls.