[RP-HPLC determination of 1-(p-methylphenyl-2-(2-piperidinoacetyl- 1,2,3,4-tetrahydroisoquinoline hydrochloride in rabbit plasma and its pharmacokinetic parameters].
A reversed phase high performance liquid chromatographic method (RP-HPLC) was developed for the determination of rabbit plasma levels of 1-(p-methylphenyl-2-(2-piperidinoacetyl)-1, 2, 3, 4-tetrahydroisoquinoline hydrochloride (70026), a new antiarrhythmic agent with promising prospects. Its pharmacokinetic parameters were obtained from the rabbit plasma level-time curve measured. 70026 plasma sample was determined by extracting with ether and 0.2 mol/L sulfuric acid, chromatographing on LiChrosorb RP-C18 column, and detecting at 230 nm. The mobile phase selected was methanol-water-triethylamine-phosphoric acid (63:37:1:0.8 v/v). The average recovery of the entire procedure from plasma was 99.94 +/- 3.10 (SD) %; the average CV of within-day and between-day were 4.12% and 3.95% respectively; the minimum detection limit was 3 ng; 70026 plasma concentration ranging from 25-2000 ng/ml yielded a good linear relationship with the peak area ratios, Y = 0. 002865X-0.01346, r = 0. 9999. No endogeneous interference was found in chromatograms of plasma sample. The purity of chromatographic peak of 70026 was identified and proved by mass spectrometry. In urine sample, the hydrolysate of 70026 was found as the original and bound forms. The rabbit plasma level of 70026 after intravenous administration versus time curve was found to be in correspondence with two-compartment model, T1/2 = 4.80 + 1.522 (h).
Xie
X Y
XY
School of Pharmacy, Shanghai Medical University.
Cheng
W B
WB
Zhou
Z S
ZS
Qin
Z L
ZL
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D007546:Isoquinolines / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D010880:Piperidines / Q000097:blood / Q000493:pharmacokinetics*; D011817:Rabbits; D044005:Tetrahydroisoquinolines
D000889:Anti-Arrhythmia Agents; D007546:Isoquinolines; D010880:Piperidines; D044005:Tetrahydroisoquinolines; C073853:toquipidine