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The determination of diflucortolone in rabbit plasma by liquid chromatography-tandem mass spectrometry (LC-MS/MS)
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Hua-jiao YANG1, 2, Li-nan WU2, Yan-ping LIU2, Yuan GU2, Guang-li WEI2, Wan-hui LIU1, Duan-yun SI2, *
Acta Pharmaceutica Sinica | 2019, 54(3) : 522 - 527
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Acta Pharmaceutica Sinica | 2019, 54(3): 522-527
Original Articles
The determination of diflucortolone in rabbit plasma by liquid chromatography-tandem mass spectrometry (LC-MS/MS)
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Hua-jiao YANG1, 2, Li-nan WU2, Yan-ping LIU2, Yuan GU2, Guang-li WEI2, Wan-hui LIU1, Duan-yun SI2, *
Affiliations
  • 1. Yantai University, Yantai 246000, China
  • 2. State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China
Published: 2019-03-12 doi: 10.16438/j.0513-4870.2018-0816
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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.

diflucortolone  /  LC-MS/MS  /  percutaneous administration  /  corticosteroids  /  pharmacokinetics
Hua-jiao YANG, Li-nan WU, Yan-ping LIU, Yuan GU, Guang-li WEI, Wan-hui LIU, Duan-yun SI. The determination of diflucortolone in rabbit plasma by liquid chromatography-tandem mass spectrometry (LC-MS/MS)[J]. Acta Pharmaceutica Sinica, 2019 , 54 (3) : 522 -527 . DOI: 10.16438/j.0513-4870.2018-0816
Year 2019 volume 54 Issue 3
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Article Info
doi: 10.16438/j.0513-4870.2018-0816
  • Receive Date:2018-09-04
  • Online Date:2026-01-26
  • Published:2019-03-12
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History
  • Received:2018-09-04
  • Revised:2018-12-05
Funding
Affiliations
    1. Yantai University, Yantai 246000, China
    2. State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China
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表12种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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