Application of automated dried blood spot sampling and LC-MS/MS for pharmacokinetic studies of AMG 517 in rats.
BACKGROUND
The use of dried blood spot (DBS) sampling technique is of particular interest for drug discovery pharmacokinetic studies due to the small blood volume requirement. In addition, automated blood sampling is an attractive approach for rat pharmacokinetic studies as animal handling work is minimized. The goal of this study was to use an automated DBS sampler for automated blood collection and spotting onto DBS paper for pharmacokinetic studies in rats. AMG 517, a potent and selective vanilloid receptor antagonist, was dosed to rats (n = 3) intravenously and blood samples were collected at nine time points over a 24 h period using the automated DBS sampler. After drying, storage and shipment, the DBS samples were extracted and analyzed by LC-MS/MS.


RESULTS
The developed bioanalytical method for the analysis of DBS samples had good accuracy and precision within the context of a discovery, non-GLP analysis. The concentration-time data and pharmacokinetic parameters generated from automated spotted samples were very similar to those derived from manually spotted DBS samples. The manual DBS data were also comparable to plasma data after correction for blood-to-plasma ratio.


CONCLUSIONS
The automated DBS sampling is a promising technique for rodent pharmacokinetic studies and will improve the efficiency and quality of DBS sampling.
Department of Pharmacokinetics & Drug Metabolism, Amgen, South San Francisco, CA 94080, USA.
Craig
C
Uyeda
Roger
R
Pham
Stacy
S
Fide
Kirk
K
Henne
Guifen
G
Xu
Marcus
M
Soto
Christopher
C
James
Philip
P
Wong
D000818:Animals; D001331:Automation; D052160:Benzothiazoles / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D059788:Dried Blood Spot Testing; D008297:Male; D010599:Pharmacokinetics; D011743:Pyrimidines / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D053719:Tandem Mass Spectrometry
D052160:Benzothiazoles; C523409:N-(4-(6-(4-trifluoromethylphenyl)pyrimidin-4-yloxy)benzothiazol-2-yl)acetamide; D011743:Pyrimidines; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat