title: HPLC determination and steady-state bioavailability study of levodropropizine sustained-release tablets in dogs.
abstract: A simple HPLC method using UV detection was developed and validated for the determination of levodropropizine (LDP) in dog plasma. The sample was prepared for injection using a liquid-liquid extraction method with 1-phenypiperazine as the internal standard. The mobile phase was methanol-diethylamine solution (0.05 M) (20:80, v/v, pH adjusted to 3.0 with H3PO4) with a detection wavelength of 240 nm. The limit of quantitation (LOQ) of LDP in a biological matrix was determined to be 25.25 ng/mL. The calibration curve was linear across the concentration range of 25.25 to 2020 ng/mL. The intra-day and inter-day precision values (CV %) were within 7% and accuracy (R.E. %) was within 6% of the nominal values for medium (252.5 ng/mL) and high (2020 ng/mL) LDP concentrations. For the LDP concentration at the LOQ, the intra-day and inter-day precision and accuracy were within 20% and 10%, respectively. The average absolute recovery for LDP was 70.28%. This method was successfully used to analyze plasma samples in a steady-state bioavailability study of a newly developed sustained-release LDP tablets (SR) using immediate-release tablets (IR) as the reference. The relative bioavailability of the SR was determined to be 106.3 +/- 12.8% (n=6). The Cmax of the SR was significantly lower (P<0.05), and the tmax was significantly longer than that of the IR (P<0.05). The results of ANOVA and two one-sided tests indicated that the SR exhibited acceptable sustained release properties and was bioequivalent to the IR.
authors.affiliation: Center For Drug Reevaluation, State Food and Drug Administration, Beijing, China. yanlin@cdr.gov.cn
authors.forename: Lin
authors.initials: L
authors.lastname: Yan
authors.forename: Tongling
authors.initials: T
authors.lastname: Li
authors.forename: Rongqin
authors.initials: R
authors.lastname: Zhang
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Xu
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000996:Antitussive Agents / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003692:Delayed-Action Preparations; D004285:Dogs; D011409:Propylene Glycols / Q000097:blood / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet; D013607:Tablets
chemical_list: D000996:Antitussive Agents; D003692:Delayed-Action Preparations; D011409:Propylene Glycols; D013607:Tablets; C035916:dipropizine