A high throughput dried DMSO LogD lipophilicity measurement based on 96-well shake-flask and atmospheric pressure photoionization mass spectrometry detection.
A rapid throughput octanol-water lipophilicity measurement based on 96-well shake-flask and LC/UV/APPI/MS is described. The method utilizes central liquid storage where compounds are stored as 10 mM solutions in dimethyl sulfoxide (DMSO). The DMSO is subsequently removed to generate solid like material used for LogD measurement. The removal of DMSO minimizes the concern for potential DMSO cosolvent effect on the measured value. Sample preparation is automated using a liquid handling workstation with 96-well pipetter. Both octanol and buffer phases are quantified using state of the art ultra-high pressure HPLC coupled with a superficially diffused core reversed-phase column and an atmospheric pressure photo ionization mass spectrometer. The throughput of the method is two days for a batch of 96 compounds. The method has been validated using 72 literature compounds with diverse ionization and LogD values ranging from -2 to +6. The observed coefficient of determination r(2) is 0.9973.
Alelyunas
Yun W
YW
CNS Chemistry Department, AstraZeneca Pharmaceuticals LP, 1800 Concord Pike, PO Box 15437, Wilmington, DE 19850-5437, USA. yun.alelyunas@astrazeneca.com
Pelosi-Kilby
Luciana
L
Turcotte
Pascal
P
Kary
Mary-Britt
MB
Spreen
Russell C
RC
D001274:Atmospheric Pressure; D002021:Buffers; D002853:Chromatography, Liquid; D004121:Dimethyl Sulfoxide / Q000737:chemistry*; D057166:High-Throughput Screening Assays / Q000295:instrumentation* / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D007477:Ions; D013058:Mass Spectrometry / Q000295:instrumentation* / Q000379:methods*; D008956:Models, Chemical; D000442:Octanols / Q000737:chemistry; D015203:Reproducibility of Results; D014466:Ultraviolet Rays
D002021:Buffers; D007477:Ions; D000442:Octanols; D004121:Dimethyl Sulfoxide