高效液相色谱-电喷雾电离串联质谱法(HPLC-ESI-MS/MS)定量测定人血浆中3α-羟基替布洛酮:在健康绝经后志愿者生物等效性研究中的应用

Lucas Azevedo Portela , Tiago Luders Laurito , Beatrice Severino , Elisa Perissutti , Gustavo D. Mendes , Ronilson Agnaldo Moreno , Gilberto De Nucci
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引用次数: 3

摘要

建立了以氘化3α-羟基替布洛酮(d5)为内标,快速、灵敏、特异地定量人血浆中3α-羟基替布洛酮的方法。采用乙醚/己烷(50/50,v/v)和氢氧化铵(50%)液-液萃取法,从血浆(900 μL)中提取分析物和内标物。采用高效液相色谱-电喷雾电离串联质谱法对提取物进行分析,无衍生化反应。色谱柱为Gemini-NX™C18 5 μm (150 × 4.6 mm直径)。该方法色谱运行时间为3.75 min,在1 ~ 100 ng/mL范围内具有线性校准曲线。定量验证限为1 ng/mL。采用该方法评价两种不同的替博龙口服制剂的生物等效性:以巴西Biolab Sanus Farmacêutica公司生产的Livolon (1.25 mg片剂)为试验制剂,以巴西Libbs Farmacêutica公司生产的Libiam™(1.25 mg片剂)为参比制剂。对46名绝经后健康女性志愿者分别给予每种配方3.75 mg的单剂量。该研究采用开放、随机、两期交叉平衡设计,两剂之间有2周的洗脱间隔。Cmax、AUC(0-last)和AUC(0-inf)个体试验/参考比的90%置信区间分别为97.48 ~ 111.51、95.35 ~ 103.20和96.42 ~ 103.86。结论是Livolon (1.25 mg片剂)与Libiam™(1.25 mg片剂)在吸收率和吸收率方面具有生物等效性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Quantification of 3α-hydroxytibolone in human plasma by high performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS): Application in a bioequivalence study in healthy postmenopausal volunteers

A sensitive, specific and fast method to quantify 3α-hydroxytibolone in human plasma using deuterated 3α-hydroxytibolone (d5) as internal standard is described. The analyte and the internal standard were extracted from plasma (900 μL) by liquid-liquid extraction using ethyl ether/hexane (50/50, v/v) and ammonium hydroxide (50%). The extracts were analyzed by high performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry without derivatization. Chromatography was performed isocratically on a Gemini-NX™ C18 5 μm (150 × 4.6 mm i. d.) column. The method had a chromatographic run time of 3.75 min and a linear calibration curve over the range 1–100 ng/mL. The limit of quantification validated was 1 ng/mL. This method was used to assess the bioequivalence between two different tibolone oral formulations: Livolon (1.25 mg tablet) provided by Biolab Sanus Farmacêutica (Brazil), as the test formulation, and Libiam™ (1.25 mg tablet) produced by Libbs Farmacêutica (Brazil), as the reference formulation. A single 3.75 mg dose of each formulation was administered to 46 postmenopausal female healthy volunteers. The study was conducted in an open, randomized, two-period crossover balanced design with a 2 week washout interval between the doses. The 90% confidence interval for Cmax, AUC(0-last) and AUC(0-inf) individual test/reference ratios were 97.48–111.51, 95.35–103.20 and 96.42–103.86, respectively. It is concluded that Livolon (1.25 mg tablet) is bioequivalent to Libiam™ (1.25 mg tablet), with regards to both rate and extent of absorption.

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