High-throughput solubility assay

Solubility and permeability were measured by a high throughput solubility assay and parallel artificial membrane permeation assay (PAMPA), respectively [56], The assays categorized 14 out of 18 drugs based on the BCS consistent with their known solubility and permeability characteristics [56],... 

Obata K, Sugano K, Machida M, Aso Y (2004) Biopharmaceutics classification by high throughput solubility assay and PAMPA. Drug Dev Ind Pharm 30 181-185. 

Figure 2.4 Correlation between the solubility of the test set obtained from the solid solubility assay (x-axis) and from the high-throughput solubility assay (y-axis average of four experiments). The black line is the 1 1 line. Symbol represents in-house compounds. Symbol O represents commercial compounds 1 - disulfiram, 2 - diethylstilbestrol, 3 -...

The next section describes the utilization of //PLC for different applications of interest in the pharmaceutical industry. The part discusses the instrumentation employed for these applications, followed by the results of detailed characterization studies. The next part focuses on particular applications, highlighting results from the high-throughput characterization of ADMET and physicochemical properties (e.g., solubility, purity, log P, drug release, etc.), separation-based assays (assay development and optimization, real-time enzyme kinetics, evaluation of substrate specificity, etc.), and sample preparation (e.g., high-throughput clean-up of complex samples prior to MS (FIA) analysis). 

FIGURE I Schematic diagram of high-throughput LC/UV/MS analysis for equilibrium solubility assay. ... 

Solubility screens using LC/MS detection do not require an ultra-pure sample of the test compound due to the selective detection of the mass spectrometer. Mass spectrometric detection offers high selectivity and low detection limits, which eliminates the need to develop complex chromatographic methods. The LC/MS-based solubility screen surpasses the traditional HPLC/UV-based equilibrium solubility assay with increased throughput, minimal manual intervention, and high sensitivity and selectivity. 

Zhou, L., Yang, L., Tilton, S. and Wang, J. (2007) Development of a high throughput equilibrium solubility assay using miniaturized shake-flask method in early drug discovery. Journal of Pharmaceutical Sciences, 96, 3052-3071. 

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