Parallel high-throughput accurate mass measurement using a nine-channel multiplexed electrospray liquid chromatography ultraviolet time-of-flight mass spectrometry system.
A nine-channel multiplexed electrospray (MUX) liquid chromatography ultraviolet time-of-flight mass spectrometry (LC/UV/TOFMS) system has been used to simultaneously measure accurate masses of eluting components from eight parallel gradient LC columns. Accuracies better than 5 and 10 ppm were achieved for 50 and 80% of samples, respectively, from a single batch analysis of ten plates (960 samples) of a Fmoc-Asp(OtBu)-OH and reserpine mixture. Combinatorial library compounds were analyzed using this parallel high-throughput system in both positive and negative modes to rigorously verify expected products and identify side products. A mass accuracy of 10 ppm root mean square (RMS) is routinely obtained for combinatorial library samples from this high-throughput accurate mass LC/MS system followed by automated data processing. This mass accuracy is critical in revealing combinatorial synthesis problems that would be missed by unit mass measurement.
Fang
Liling
L
ChemRx Division, Discovery Partners International, 385 Oyster Point Blvd. Suite # 1, South San Francisco, CA 94080, USA. Fang@chemrx.com
Demee
Michael
M
Cournoyer
Jason
J
Sierra
Teresa
T
Young
Connie
C
Yan
Bing
B
D000409:Alanine / Q000032:analysis; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D004743:Enkephalin, Leucine / Q000032:analysis; D008970:Molecular Weight; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013997:Time Factors
D004743:Enkephalin, Leucine; D000409:Alanine