TY - JOUR
T1 - Novel high-performance liquid chromatographic assay using fluorescence detection for the quantitation of plasma γ-methylene-10-deazaaminopterin and its major metabolite, 7-hydroxy-γ-methylene-10 -deazaaminopterin, in patients with solid cancers in a phase I trial
AU - Su, H.
AU - Chen, T. L.
AU - Hausheer, F. H.
AU - Rowinsky, E. K.
PY - 1997/8/1
Y1 - 1997/8/1
N2 - γ-Methylene-10-deazaaminopterin (MDAM), a unique dihydrofolate reductase inhibitor, has demonstrated antitumor activity against a broad spectrum of human solid tumors in preclinical studies. A novel reversed-phase, ion-pair high-performance liquid chromatography (HPLC) assay that uses fluorescence detection has been developed to quantitate levels of MDAM and its major metabolite, 7-hydroxy-γ-methylene-10-deazaaminopterin (7-OH-MDAM), in human plasma. The recovery of MDAM and 7-OH-MDAM from plasma was >97% by a simple one-step deproteinization process using tetrabutylammonium bromide (TBABr) and methanol. MDAM and 7-OH-MDAM remained stable in plasma over a 28-day test period at ambient temperatures, and neither compound was light-sensitive. The limit of quantitation was 0.005 μM for both MDAM and 7-OH-MDAM. This assay has been found to be simple, sensitive and reproducible in determining plasma concentrations of MDAM and 7-OH-MDAM in patients with solid cancers in a phase trial.
AB - γ-Methylene-10-deazaaminopterin (MDAM), a unique dihydrofolate reductase inhibitor, has demonstrated antitumor activity against a broad spectrum of human solid tumors in preclinical studies. A novel reversed-phase, ion-pair high-performance liquid chromatography (HPLC) assay that uses fluorescence detection has been developed to quantitate levels of MDAM and its major metabolite, 7-hydroxy-γ-methylene-10-deazaaminopterin (7-OH-MDAM), in human plasma. The recovery of MDAM and 7-OH-MDAM from plasma was >97% by a simple one-step deproteinization process using tetrabutylammonium bromide (TBABr) and methanol. MDAM and 7-OH-MDAM remained stable in plasma over a 28-day test period at ambient temperatures, and neither compound was light-sensitive. The limit of quantitation was 0.005 μM for both MDAM and 7-OH-MDAM. This assay has been found to be simple, sensitive and reproducible in determining plasma concentrations of MDAM and 7-OH-MDAM in patients with solid cancers in a phase trial.
KW - γ-Methylene-10-deazaaminopterin
KW - 7-hydroxy-γ-methylene-10-deazaaminopterin
UR - http://www.scopus.com/inward/record.url?scp=0030877275&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030877275&partnerID=8YFLogxK
U2 - 10.1016/S0378-4347(97)00205-3
DO - 10.1016/S0378-4347(97)00205-3
M3 - Article
C2 - 9300877
AN - SCOPUS:0030877275
SN - 1572-6495
VL - 695
SP - 401
EP - 408
JO - Journal of Chromatography B: Biomedical Applications
JF - Journal of Chromatography B: Biomedical Applications
IS - 2
ER -