Simultaneous determination of buprenorphine and its prodrug, buprenorphine propionate, by high-performance liquid chromatography with fluorescence detection: application to pharmacokinetic studies in rabbits.
A rapid, sensitive, precise and accurate high-performance liquid chromatographic assay with fluorescence detection was developed for the simultaneous determination of buprenorphine and buprenorphine propionate in human and animal blood. Buprenorphine propionate was also proven to be a prodrug of buprenorphine. It was comprised of only a one-step extraction procedure with ethyl acetate and normal-phase chromatography on a Betasil Silica column. The recoveries of buprenorphine and buprenorphine propionate were above 84%. Calibration graphs were linear for buprenorphine over the concentration range 2-1500 ng/ml and for buprenorphine propionate over the concentration range 20-1500 ng/ml with a coefficient of variation, both within- and between-day, or less than 10% at any level. The limits of quantitation of buprenorphine and buprenorphine propionate in human or animal blood were 2.0 and 20 ng/ml, respectively, based on a single-to-noise ratio of 3. The method has been successfully applied to pharmacokinetic studies of buprenorphine and buprenorphine propionate in rabbits. The results demonstrated that buprenorphine propionate was rapidly and totally converted to its parent drug, buprenorphine, following intravenous administration. Buprenorphine propionate is a prodrug of buprenorphine.
Liu
Shyun-Yeu
SY
Department of Oral and Maxillofacial Surgery, National Defense Medical Center, Taipei/Chi-Mei Medical Center, No. 901, Chung-Hwa Road, Yung-Kang, Tainan, Taiwan, ROC. 400003@mail.chimei.org.tw
Liu
Kuo-Sheng
KS
Kuei
Chun-Hsiung
CH
Tzeng
Jann-Inn
JI
Ho
Shung-Tai
ST
Wang
Jhi-Joung
JJ
D000818:Animals; D002047:Buprenorphine / Q000097:blood* / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D008297:Male; D011355:Prodrugs / Q000032:analysis*; D011817:Rabbits; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence
D011355:Prodrugs; D002047:Buprenorphine