Sensitive and high-throughput isomer-specific analysis of human milk oligosaccharides using UPLC-MS/MS and its application to secretor status assignment.

Human milk oligosaccharides (HMOs) are now the principal component of the latest infant formula generation. However, it is challenging to separate and quantify highly heterogeneous isomers when analyzing HMOs. Here, we developed a high-throughput isomer-resolved quantification method for 21 native HMOs based on ultrahigh-performance liquid chromatography-mass spectrometry-multiple reaction monitoring (UPLC-MS-MRM) technology.

Accurate prediction of K based on experimental measurement of K and computed physicochemical properties of candidate compounds in CNS drug discovery.

A mathematical equation model was developed by building the relationship between the f/f ratio and the computed physicochemical properties of candidate compounds, thereby predicting K based on a single experimentally measured K value. A total of 256 compounds and 36 marketed published drugs including acidic, basic, neutral, zwitterionic, CNS-penetrant, and non-CNS penetrant compounds with diverse structures and physicochemical properties were involved in this study. A strong correlation was demonstrated between the f/f ratio and physicochemical parameters (CLogP and ionized fraction).

High-throughput screening of LogD by using a sample pooling approach based on the traditional shake flask method.

A new approach for screening LogD is presented. The method is based on the shake flask method combined with rapid generic LC-MS/MS bioanalysis by using a sample pooling approach that enables high-throughput screening of LogD or LogP in the drug discovery stage. The method is evaluated by a comparison of measured LogD between single and pooled compounds for a test set of structurally diverse compounds with a wide range of LogD values (from -0.