High-throughput purification platform in support of drug discovery.
The application of parallel synthesis is an efficient approach to explore the chemical space and to rapidly develop meaningful structure activity relationship (SAR) data for drug discovery programs. However, the effectiveness of the parallel synthesis requires a high throughput purification workflow that can process a large number of crude samples within a meaningful time frame. This paper describes a high throughput purification platform that has been adopted at Merck's Rahway research site. The platform includes the evaluation of crude samples, mass-directed HPLC purification, fraction analysis, compound registration, final compound purity assessment and assay distribution. Assisting with the sample tracking and the data management is the internally designed laboratory information management system, Light Automation Framework (LAF). Using this process and the tools described herein, the group has successfully achieved purities of 95% or greater for 90% of samples.
Merck & Company, Rahway, New Jersey 07065, United States. min_liu@merck.com
Min
M
Liu
Kuanchang
K
Chen
Denny
D
Christian
Tazeen
T
Fatima
Natalya
N
Pissarnitski
Eric
E
Streckfuss
Chaowei
C
Zhang
Lei
L
Xia
Scott
S
Borges
Zhicai
Z
Shi
Petr
P
Vachal
James
J
Tata
John
J
Athanasopoulos
D002851:Chromatography, High Pressure Liquid; D055808:Drug Discovery / Q000295:instrumentation / Q000379:methods*; D004867:Equipment Design; D057166:High-Throughput Screening Assays / Q000295:instrumentation / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification*; D011786:Quality Control; D013329:Structure-Activity Relationship
D004364:Pharmaceutical Preparations