Increasing the efficiency of pharmacokinetic sample procurement, preparation and analysis by liquid chromatography/tandem mass spectrometry.
The movement towards a 96-well format has greatly increased productivity and throughput in bioanalytical laboratories. Improvements in automated sample preparation and analytical methods have further contributed to increased productivity. We have focused on sample collection and transfer to the bioanalyst and have found improvements to the current available methods. The problem of manual transfers and plasma clotting issues can be overcome with the use of microtainers. Specifically, for illustrative purposes, three proprietary Theravance compounds were tested for stability, non-specific binding, and electrospray ion suppression in microtainers. There were no issues with stability, non-specific binding or ion suppression for the above compounds even after leaving plasma samples in the microtainers over long periods of time. The microtainers are robot-compatible and the resulting plasma can be transferred without clotting issues. To date, all in-house compounds successfully analyzed and tested using the microtainers have mass ranges between 200 and 1800 Da, pK(a) ranges between 3.8 and 10.3, and logD ranges between -1.7 and 4.2. Once samples are transferred into 96-well plates, flexibility in preparation and analysis is available. Together with automated sample preparation and the use of liquid chromatography/tandem mass spectrometry (LC/MS/MS) as an analytical tool, the use of microtainers as sample collection tubes and for sample storage saved considerable time, cost and effort in both of our pharmacokinetic (PK) and bioanalytical groups. This in turn has led to an increased efficiency and overall throughput in support of our drug discovery effort.
Villa
Josephine S
JS
Department of Analytical Chemistry, Theravance, Inc., 901 Gateway Blvd., South San Francisco, CA 94080, USA. jvilla@theravance.com
Cass
Robert T
RT
Karr
Dane E
DE
Adams
Stacy M
SM
Shaw
Jeng-Pyng
JP
Schmidt
Donald E
DE
D000818:Animals; D001331:Automation; D001774:Blood Chemical Analysis / Q000379:methods / Q000592:standards; D002853:Chromatography, Liquid / Q000379:methods; D010599:Pharmacokinetics; D011786:Quality Control; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods* / Q000592:standards