Some Thoughts about High-throughput Analytical Chemistry

Some Thoughts about High-throughput Analytical Chemistry 

Analysts like to make chemical measurements to the highest quality they can, and this is possible with modem instrumentation and good analytical practice. Chemical parameters are generally measured more accurately and reproducibly than parameters measured in biological systems, and the results are more reliable than values calculated by software from structure alone (e.g., calculated log P, pKa). Of all the information available to medicinal chemists, measured chemical parameters are probably the most reliable. With these thoughts in mind, it makes sense not to 

All measurements in duplicate except acyclovir (x3) and labetalol (x5). Results obtained by First Derivative (FD) or Target Factor Analysis (TFA). 

Note that it is highly desirable that the identity of every sample is confirmed before analysis, and that samples are adequately pure for the measurement in question. In the pH-metric methods, the sensor is a pH electrode and cannot distinguish between analyte and impurity. In the methods that depend on UV absorbance, if a sample contains an impurity with stronger absorbance than the sample, then the calculation of results from experimental data is complicated. Combinatorial samples are by nature poorly characterized, and even in the chromatographic methods in which analyte and impurity will be separated, it may be difficult to assign the peaks unambiguously. It is therefore advisable to purify samples before they are submitted for analysis of log D and pKa. 

All of the methods described and referenced here are capable of producing high-quality, accurate results, but only if the raw data are correctly interpreted and analyzed to detect (and correct) for issues arising from issues such as low solubility, ion pair partition or multiple ionizable groups with overlapping pKas. It is not 

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