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Archive > Volume 3 Issue 2 > 2011,3(2):144-149. DOI:10.3969/j.issn.1674-6384.2011.02.010 Prev Next

Validated LC- MS/MS assay for the determination of wogonin: Application to a preclinical pharmacokinetics and bioavailability of different wogonin administration in beagle dogs

Original articles

Study on Plasma Concentration and Bioavailability of Wogonin in Beagle’s Dogs

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    摘要:
    摘要 目的: 建立比格犬血漿中漢黃芩素血藥濃度的檢測方法，研究漢黃芩素不同給藥形式在比格犬體內(nèi)的生物利用度； 方法: 6只比格犬采用三交叉設(shè)計(jì)，不同周期分別給予漢黃芩素靜脈給藥、灌胃給予原料藥及口服溶液劑。血漿樣品經(jīng)乙酸乙酯液-液萃取后，LC-MS/MS法測定血漿中的藥物濃度，最低定量下限（LLOQ）為0.105 μg/L，檢測離子分別為漢黃芩素 m/z 285.0→270.0，內(nèi)標(biāo)（非那雄胺）m/z 373.3→305.3. 藥代動力學(xué)參數(shù)采用DAS 軟件 (Ver 2.0)進(jìn)行分析.

    Abstract:
    Objective To develop an LC-MS/MS method for determining the concentration of wogonin in dog plasma and investigate the pharmacokinetics and bioavailability by different administrations of wogonin in Beagle’s dogs. Methods LC-MS/MS was employed in determining the concentration of wogonin with the selected ion monitoring model after liquid-liquid extraction with ethyl acetate of dog plasma samples. The lower limit of quantification was 0.105 μg/L. Target ions were at m/z 285.0→270.0 for wogonin and 373.3→305.3 for finasteride. In a randomized, self-control, and cross-over study, six male Beagle’s dogs were treated with different administration methods in three test periods. Pharmacokinetic parameters were calculated with DAS software (Ver. 2.0). Results The calibration curve was linear in the range of 0.105－107.36 μg/L for wogonin in dog plasma samples. The main pharmacokinetic parameters of ig administration (native drug of 15 mg/kg and solution preparation of 5 mg/kg) and iv route were as follows: Cmax (2.5 ± 1.1), (7.9 ± 3.3), and (6838.7 ± 1322.1) μg/L, tmax (0.7 ± 0.3) and (0.3 ± 0.2) h for the both former, AUC0-t (7.1 ± 2.0), (21.0 ± 3.2), and (629.7 ± 111.8) μg?h/L. The absolute bioavailability of native and solution of wogonin were (0.59 ± 0.35)% and (3.65 ± 2.00)%, respectively. Conclusion The validated method is convenient, sensitive, and specific, and the improvement of wogonin solubility could remarkably increase the absolute bioavailability.

    關(guān)鍵詞:
    生物利用度; 比格犬; 高效液相色譜-質(zhì)譜聯(lián)用法; 漢黃芩素

    Keywords:


    Project Supported:
    the Colleges and Universities Natural Science Foundation of Anhui Province (KJ2009B216Z)

    Clc Number:

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