The effects of thermal pretreatments at 180, 400, and 840 °C on the subsequent chemical modification of silica gel have been characterized by heterogeneous gas-solid chromatography (HGSC) and Infrared spectroscopy. Silica gel treated at 400 °C exhibited a surface area, surface polarity, and surface selectivity similar to those of the same material treated at 180 °C, even though the 400 °C gel could be modified to a much greater extent by gas-phase sllanization with hexamethyldlsllazane. The HGSC and IR results taken together Indicate that there are strongly hydrogen-bonded surface hydroxyl species on silica gel (sllanols or bound water), which are Inactive with regard to physical adsorption but which prevent complete stoichiometric modification of the silica surface. These Inactive sllanols can be removed with heating at elevated (>200 °C) temperatures, suggesting that thermal pretreatment of the silica support can be utilized to make more homogeneous and therefore more efficient bonded liquid chromatography stationary phases. Thermal treatment at 840 °C produces a silica gel with free (nonbound) Internal sllanols and external sllanols that can be completely modified with surface ligands, but the sintering that occurs at this temperature reduces the surface area of the silica gel such that It is no longer chromatographically useful.

A polarity scale for heterogeneous surfaces Is proposed that uses energy distribution functions calculated from chromatographic retention data. The energy required to form a complete monolayer (E^), obtained from the energy distribution

A powder X-ray diffraction method was developed and validated to measure the crystalline impurity 4-(5-cyclopentyloxy-carbonylamino-1-methyl-indol-3-ylmethyl)-3-methoxy-N-o-tolylsulfonylbenzamide hydrate in a pharmaceutical tablet ranging from 0.6 to 3% (w/w). The calibration plot was found to be linear with a correlation coefficient (r2) of 0.996, and was reproducible among operators. The detection limit was determined to be 0.6% with a signal-to-noise ratio of 3:1. The quantitation limit was determined to be 1% with a signal-to-noise ratio of 5:1. Instrument precision at the quantitation limit was 5.8%. Method precision was 6.1% at the quantitation limit and 7.4% at the detection limit. Intermediate precision at the quantitation limit was 7.3% during a 6-month study. Accuracy measurements using crystalline impurity standards prepared in an excipient mixture ranged from 89.3 to 105.5%. Accuracy measurements using tablets containing spiked quantities of crystalline impurity ranged from 72.0 to 92.7%. Accuracy measurements using spiked tablets were complicated because the crystalline impurity was lost during the manufacturing process and a correction factor was used. Ruggedness was assessed by evaluating repetitive assay, repetitive packing, sample packing, and sample stability. Repetitive assays show the exposure of standards to a relative humidity in excess of 57% caused displacement error because of an increase in sample volume and a peak-position shift. Repetitive-packing studies show the analyte was extracted from the sample at a low relative humidity because of a static-charge induction. Sample-packing studies show that two subjective packing techniques were equivalent, and that under- and over-packing samples cause changes in sample density which would not affect results within ±16%. Sample-stability studies show that the quantitation-limit standard was stable as long as the sample was exposed to a relative humidity below 57%.