TY - JOUR
T1 - Supercritical fluid chromatography for therapeutic drug monitoring of immunosuppressants
T2 - Selectivity for cyclosporine a, fk 506 (tacrolimus), and rapamycin
AU - Wong, Steven H.Y.
AU - Ghodgaonkar, Bharti
AU - Fong, Peter
AU - Campbell, Brendan
AU - Burdick, F. James
AU - Boctor, Fouad
PY - 1994/6/1
Y1 - 1994/6/1
N2 - Clinical monitoring of cyclosporine A (CsA) in whole blood is currently performed by either immunoassays or high-performance liquid chromatography. A new immunosuppressant, FK 506 -Tacrolimus, is currently undergoing multi-centers clinical trial for liver transplant, while active research and clinical studies are being performed for another new immunosuppressant, raparnycin. The present study investigated their chromatographic selectivities by supercritical fluid chromatography, in comparison to HPLC. Feasibility studies were performed for the analyses of extracts of whole blood samples, after solid-phase extraction. SFC analyses were performed by using an open tubular SB-biphenyl capillary column, C02as the mobile phase, pressure programming from 100 to 300 atmospheres, separation temperature of 70® C, and FID detection. CsA eluted after the internal standard CsD, while FK 506 tautomer eluted after FK 506. From the “ reversal’’ of elution order as compared to reversed-phase LC, the selectivity of the above column with CO2 as the mobile phase was characterized as “ normal-phase HPLC-like “. Analysis of extracts of CsA patient’s samples, and FK 506 spiked whole blood samples showed that the current SFC procedure did not achieve sufficient sensitivity limit for clinical therapeutic drug monitoring.
AB - Clinical monitoring of cyclosporine A (CsA) in whole blood is currently performed by either immunoassays or high-performance liquid chromatography. A new immunosuppressant, FK 506 -Tacrolimus, is currently undergoing multi-centers clinical trial for liver transplant, while active research and clinical studies are being performed for another new immunosuppressant, raparnycin. The present study investigated their chromatographic selectivities by supercritical fluid chromatography, in comparison to HPLC. Feasibility studies were performed for the analyses of extracts of whole blood samples, after solid-phase extraction. SFC analyses were performed by using an open tubular SB-biphenyl capillary column, C02as the mobile phase, pressure programming from 100 to 300 atmospheres, separation temperature of 70® C, and FID detection. CsA eluted after the internal standard CsD, while FK 506 tautomer eluted after FK 506. From the “ reversal’’ of elution order as compared to reversed-phase LC, the selectivity of the above column with CO2 as the mobile phase was characterized as “ normal-phase HPLC-like “. Analysis of extracts of CsA patient’s samples, and FK 506 spiked whole blood samples showed that the current SFC procedure did not achieve sufficient sensitivity limit for clinical therapeutic drug monitoring.
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U2 - 10.1080/10826079408013534
DO - 10.1080/10826079408013534
M3 - Article
AN - SCOPUS:0028167425
SN - 0148-3919
VL - 17
SP - 2093
EP - 2109
JO - Journal of Liquid Chromatography
JF - Journal of Liquid Chromatography
IS - 10
ER -