Determination of cyanide and nitroprusside in blood and plasma

A procedure was refined for quantitative isolation of cyanide by gas transfer from acidified blood or plasma samples. The cyanide was trapped in dilute alkali and quantified as the pyridine/pyrazolone complex. The within-day coefficient of variation was 2%, which increased to about 2.5% for the day-to-day variation. Nitroprusside used as a hypotensive agent in clinical medicine provides a risk of cyanide toxicity when the rate of administration or the total amount of drug given is excessive. A procedure was developed for measuring nitroprusside in the plasma of man and animals. Nitroprusside in the sample is quantitatively converted to cyanide by incubation with cystein solution at slightly alkaline pH. Methemoglobin is added to combine with the cyanide formed and prevent its destruction. On acidification, the total amount of cyanide originally present as free cyanide or as nitroprusside is liberated as HCN, isolated by gas transfer into a sodium hydroxide trap, and quantified by spectrophotometry. Nitroprusside present in the sample is calculated from the increase in cyanide observed in the cysteine-treated sample compared to that obtained without cysteine treatment. The method has been used to estimate in vitro stability of nitroprusside in aqueous solution, blood, and plasma. Blood cyanide and plasma nitroprusside concentrations were measured when sodium nitroprusside was infused into a baboon. Over 90% of the nitroprusside in blood is present in the plasma, suggesting that the drug crosses the erythrocyte membrane slowly.