Distribution of methotrexate in human blood in vitro: independence of temperature, pH and drug concentration.

Distribution of methotrexate (MTX) in blood samples from a single donor as a function of incubation time, temperature, pH and drug concentration was investigated. Equilibrium, as expressed by the cell/plasma (C/P) partition ratio, was reached rapidly and was constant for 5 to 30 min following incubation. The C/P ratio was unaffected by temperature variations in the 4 to 37 degrees C range, pH variations from 7.06 to 7.82 and varying drug concentrations from 5 X 10(-5) M to 5 X 10(-10) M. Contradicting an earlier investigation, this implies that MTX can be monitored in plasma or serum samples without undue worries about hitherto unexplained and unusual distribution kinetics for this drug in blood.