The determination of diflucortolone in rabbit plasma by liquid chromatography-tandem mass spectrometry (LC-MS/MS)
10.16438/j.0513-4870.2018-0816
- VernacularTitle:LC-MS/MS法测定家兔血浆中二氟可龙的浓度
- Author:
Hua-jiao YANG
1
,
2
;
Li-nan WU
3
;
Yan-ping LIU
3
;
Yuan GU
3
;
Guang-li WEI
3
;
Wan-hui LIU
1
;
Duan-yun SI
3
Author Information
1. Yantai University, Yantai 246000, China
2. State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China
3. State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China
- Publication Type:Research Article
- Keywords:
iflucortolone;
LC-MS/MS;
percutaneous administration;
corticosteroids;
pharmacokinetics
- From:
Acta Pharmaceutica Sinica
2019;54(3):522-527
- CountryChina
- Language:Chinese
-
Abstract:
A sensitive and efficient liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for quantitative determination of diflucortolone in rabbit plasma after dermal administration of diflucortolone valerate cream to rabbits. After extraction with ethyl acetate, the chromatographic separation was performed on Zorbax Eclipse XDB-C18 (50 mm×4.6 mm, 5 μm) with a gradient mobile phase consisting of 50% acetonitrile-50% methanol and 0.1% formic acid-5% methanol-5 mmol·L-1 ammonium formate at a flow rate of 0.35 mL·min-1. The quantitative analysis was carried out using multiple reaction monitoring (MRM) at specific ion transitions of m/z [M+H]+ 395.2→m/z 355.2 for diflucortolone and m/z [M+H]+ 258.1→m/z 120.9 for ethoxyphenylethylamine (internal standard) in positive ion mode with electrospray ionization (ESI) source. This validated LC-MS/MS method had a linearity over the concentration range of 0.01-10 ng·mL-1 with the lower limit of quantification (LLOQ) at 0.01 ng·mL-1. At level of LLOQ, the inter and intra-assay precision (RSD) were no greater than 9.82% and 11.0%, respectively. The main pharmacokinetic parameters of the diflucortolone including tmax, Cmax, AUC0-72 h, and t1/2 were as follows: (6.33±1.21) h, (0.168±0.080 0) ng·mL-1, (3.15±0.834) h·ng·mL-1, (32.0±17.4) h. The method was validated in the pharmacokinetic study of diflucortolone in rabbit following dermal administration of diflucortolone valerate cream at dose of 0.01 g·cm-2. In this study, the program of animal testing had been approved by Committee on the management and usage of experimental animal in the Evaluation Company of Innovative Drug, Tianjin Institute of Pharmaceutical Research.
