Determination of nalbuphine by high-performance liquid chromatography with ultraviolet detection: application to human and rabbit pharmacokinetic studies.
A rapid, sensitive, precise and accurate high-performance liquid chromatographic assay with ultraviolet detection was developed for the determination of nalbuphine in human, rabbit, pig and dog plasma. It is comprised of only a one-step extraction procedure with hexane-isoamyl alcohol at pH 9.25 and reversed-phase chromatography on a micro Porasil column. The recoveries of nalbuphine and ethylmorphine (internal standard) were greater than 86%. Calibration graphs were linear over the concentration range 0.75-150 ng/ml with a coefficient of variation, both within-day and between-day, of less than 10% at any level. The limit of quantitation was 0.75 ng/ml of plasma based on a signal-to-noise ratio of 3. Seven other clinically used analgesics were investigated to check for potential interferences and their analytical conditions. The specificity of this assay was checked with a metabolite of nalbuphine (noroxymorphine). Nalbuphine in plasma did not decompose significantly at -20 degrees C for six weeks. Pharmacokinetic application in three surgical patients and four rabbits revealed that nalbuphine followed a linear three-compartment model with two distribution phases. The two distribution and one elimination half-lives and the plasma clearance of nalbuphine were 0.9, 5.8 and 157 min and 370 ml/min in human, and 3.5, 28 and 117 min and 21 166 ml/min in rabbits.
Ho
S T
ST
Department of Anesthesiology, Tri-Service General Hospital, Taipei, Taiwan.
Wang
J J
JJ
Hu
O Y
OY
Chiang
P S
PS
Lee
S C
SC
D000700:Analgesics; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000706:statistics & numerical data; D004285:Dogs; D004355:Drug Stability; D006207:Half-Life; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D009266:Nalbuphine / Q000097:blood* / Q000493:pharmacokinetics*; D011817:Rabbits; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D000700:Analgesics; D009266:Nalbuphine