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HPLC determination of indalpine and its major metabolite in human plasma and a pharmacokinetic application
Author(s) -
Toupin L.,
Caillé G.,
Vézina M.,
Demontigny C.,
Tawashi M.
Publication year - 1987
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510080603
Subject(s) - metabolite , pharmacokinetics , urine , chemistry , chromatography , oral administration , active metabolite , high performance liquid chromatography , absorption (acoustics) , pharmacology , medicine , biochemistry , physics , acoustics
A high‐performance liquid chromatographic method using a fluorometric detector was developed for the determination of plasma concentrations of the antidepressant indalpine (I) and its major metabolite 4‐[2‐(3‐indolyl)ethyl]‐2‐piperidinone (PK). the same procedure was used to measure, in urine, levels of I and of the metabolite, either conjugated or unconjugated. The sensitivity of the assay is 5 ng ml −1 of plasma or urine for both I and PK. Mean recoveries from plasma for PK, I, and the internal standard (quinine sulfate) were 86.4, 86.8, and 88.5 per cent, respectively. Mean recovery from urine for I was 82.5%. This method was used to establish the pharmacokinetic profiles of I and PK following a single oral administration of I (100 mg) in 8 healthy volunteers. Peak plasma concentrations for I and PK were obtained in an average time of 2.1 and 2.6 h ( t max ), respectively. The mean absorption t ½ of I was 0.8 h, the mean V da 8781 and the mean clearance 581 h −1 . The mean t ½ for I and PK was 10.4 and 11.9 h, respectively. In a 12 h urine collection 3 per cent of I was excreted unchanged. No conjugated or unconjugated metabolite was found in urine samples. This method was also used to determine plasma levels 10 h post‐dose (50 mg t.i.d.) during chronic oral administration in 20 hospitalized patients. Mean plasma concentrations of I and PK post‐dose were 116 ng ml −1 and 43 ng ml −1 , respectively.