Validation of a liquid chromatographic-tandem mass spectrometric method for the measurement of (R)-1-[2,3-dihydro-2-oxo-1-pivaloylmethyl-5-(2-pyridyl)-1H-1,4-benzodiazepin-3-yl]-3-(3-methylaminophenyl)urea (YF476) in human plasma.
A sensitive and specific liquid chromatographic-tandem mass spectrometric (LC-MS-MS) method has been validated for the measurement of YF476 in human plasma. The method involves a simple liquid-liquid extraction procedure, chromatography of the extracts on a C(18) column, atmospheric pressure chemical ionisation and detection in the multiple reaction monitoring mode. The calibration line was linear over the concentration range 0.1 ng/ml (the limit of quantification) to 25.0 ng/ml. Intra- and inter-batch precision was <14% and intra- and inter-batch accuracy was <11% over the entire calibration range. The bioanalytical method is robust and has been used for the analysis of many samples from human subjects involved in early clinical studies (Phase I).
Redrup
M J
MJ
Department of Mass Spectrometry, Huntingdon Life Sciences, P.O. Box 2, Huntingdon, Cambridgeshire, PE18 6ES, UK.
Leaf
F C
FC
Miyashita
A
A
Watanabe
T
T
Higuchi
S
S
Chasseaud
L F
LF
Cheng
K N
KN
D000818:Animals; D001570:Benzodiazepinones / Q000097:blood* / Q000493:pharmacokinetics; D002138:Calibration; D004285:Dogs; D006207:Half-Life; D006727:Hormone Antagonists / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D010671:Phenylurea Compounds / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D001570:Benzodiazepinones; D006727:Hormone Antagonists; D010671:Phenylurea Compounds; C104428:YF 476