Quantification of Teprenone in Human Plasma by HPLC Coupled to Mass Spectrometry: Application to a Bioequivalence Study

• Published in: Chromatographia Vol. 65; no. 9-10; pp. 533 - 538
• Main Authors: Jin-Song, Ding, Yan-Bin, Zhou, Juan, He, Juan, Song, Zhi-Rong, Tan
• Format: Journal Article
• Language: English
• Published: Oxford Wiesbaden : Vieweg Verlag 01.05.2007; Springer
• Subjects: Analysis; bioavailability; Biological and medical sciences; Column liquid chromatography-mass spectrometry; General pharmacology; Medical sciences; Pharmacology. Drug treatments; Teprenone in human plasma; Human; Validation; Biological fluid; Atmospheric pressure; Liquid liquid extraction; Coupled method; Oral administration; HPLC chromatography; Antiulcer agent; Bioavailability; Solvent extraction; Chemical ionization; Blood; Blood plasma; Sample preparation; Column liquid chromatography-mass spectrometry; Teprenone; Teprenone in human plasma; Pharmacokinetics; Mass spectrometry; Quantitative analysis
• ISSN: 0009-5893; 1612-1112
• DOI: 10.1016/S0009-5893(07)82057-1

A rapid, sensitive, and specific method has been developed for quantification of teprenone (TEP) in human plasma. The analytes were isolated from plasma by liquid-liquid extraction with t-butyl methyl ether. The extracts were analyzed by high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS); gefarnate was used as internal standard (IS). HPLC separation of the analytes was performed on a C₁₈ column with 1:54:45 (v/v) 1% aqueous acetic acid-methanol-acetonitrile as mobile phase; the flow rate was 0.2 mL min-¹. The compounds were ionized by atmospheric-pressure chemical ionization (APCI). Calibration plots for TEP were linear in the range 20.0-2000.0 ng mL-¹; correlation coefficients were >0.9981. The average extraction efficiency for TEP was >67%, method recovery was >95%, the limit of detection (LOD) was 1.0 ng mL-¹, and the intraday and interday coefficients of variation were <7%. This HPLC-MS procedure was used to assess the bioequivalence of TEP tablet and capsule formulations. A single 150-mg dose of each formulation was administered to 18 healthy male volunteers. The study was conducted using an open, randomized, two-period crossover design with a 1-week wash-out interval. Because the 90% CI for C max and the ratios of the AUCs were all within the 80-125% range stipulated by the US Food and Drug Administration, it was concluded that the TEP tablet and capsule formulations were bioequivalent in terms of rate and extent of absorption.