Solid phase extraction as a faster alternative to HPLC: application to MS analysis of metabolic stability samples.
Due to recent advances in high throughput organic synthesis, discovery teams now need to profile increased numbers of analogs in vitro for their absorption, distribution, metabolism, and excretion (ADME) properties. Consequently, pharmaceutical companies are developing lower cost and higher throughput methods for ADME testing. As demands for metabolic stability testing have increased in our laboratory, the time required to analyze samples using high-pressure liquid chromatography-mass spectrometry (HPLC-MS) has grown rapidly and ultimately limited our data output. In this study we show that solid phase extraction-mass spectrometry (SPE-MS) is a viable alternative to HPLC-MS for monitoring small molecule stability in liver microsomes. Using the SPE-MS approach, samples can be analyzed in 24 s compared to 2.5 min on the HPLC-MS without compromising data quality, thereby alleviating the analytical bottleneck.
Inman
Brittany L
BL
Abbott Laboratories, Global Pharmaceutical Research and Development, Advanced Technology, Dept. R4CP, Bldg. AP52-N, 200 Abbott Park Road, Abbott Park, Illinois 60064, USA.
Chovan
Linda E
LE
Dandliker
Peter J
PJ
Lau
Yau Yi
YY
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004285:Dogs; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D008657:Metabolic Clearance Rate; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism*; D052616:Solid Phase Extraction / Q000379:methods*