N. Kobayashi et al., Rapid, real-time sampling of R-84760 in blood by in vivo microdialysis with tandem mass spectrometry, J PHARM B, 21(6), 2000, pp. 1233-1242
A new technique involving rapid sampling of R-84760 in real-time was achiev
ed using a combination of microdialysis (MD) and tandem mass spectrometry (
MS/MS). After collecting the analyte in real-time by MD and separating it b
y MS/MS, the ion intensities are adapted to the data without any subsequent
chromatographic separation or flow injection analysis. The R-84760 concent
ration was obtained from the plateau part of the ion intensities or the cor
rected values using an internal standard, after immersing the MD probe into
the dialysis solution containing the drug for a definite time. Since conta
mination of the ion source was prevented by using an organic solvent for th
e perfused solution, it was possible to establish a stable analysis method.
For an MD membrane of length 4 mm, the R-84760 concentration in saline was
linear over the range 5-541.1 ng/ml (r(2) = 0.9997). Moreover, the R-84760
concentration in rat whole blood was linear over the range 24.9-1868.9 ng/
ml (r(2) = 0.9993). As this method allowed the measurement of free drug con
centration in rat blood, the analysis was also able to provide data needed
for determining the protein-binding ratio. The protein-binding ratio obtain
ed from the calibration curve in saline and rat whale blood was 87-90%, whi
ch was close to the result obtained by another analysis method. The concent
ration profile of R-84760 in blood as obtained by the MD-MS/MS method corre
lated well with the concentration profile in plasma, which was simultaneous
ly monitored by LC-MS/MS. (C) 2000 Elsevier Science B.V. All rights reserve
d.