Zou Jianjun, Di Bin, Zhang Junren, Dai Li, Ding Li, Zhu Yubing, Fan Hongwei, Xiao DaWei
Department of Cardiovascular and thoracic Surgery, the First Affiliated Hospital, Soochow University, Suzhou, China.
J Chromatogr Sci. 2009 Nov-Dec;47(10):889-94. doi: 10.1093/chromsci/47.10.889.
A selective and sensitive high-performance liquid chromatography-electrospray-tandem mass spectrometry method (HPLC-ESI-MS-MS) has been developed for the determination of adefovir in human plasma using adenine (PMPA) as an internal standard. After protein precipitation with methanol, the plasma sample was separated by HPLC on a reversed-phase XTerra MS/MS C(18) column (100 mm x 2.1 mm i.d., 3.5 mm) with a mobile phase of methanol-water (20:80, v/v). Standard curves were linear (r(2) = 0.9962) over the concentration range of 0.20-100 ng/mL and had acceptable accuracy and precision. The intra- and inter-batch precisions were within 11.30%. The lower limit of quantification (LLOQ) was 0.20 ng/mL. The validated HPLC-ESI-MS-MS method has been used successfully to study the pharmacokinetics of adefovir in healthy Chinese volunteers. The following pharmacokinetic parameters were elucidated after administering a single dose of 10 mg, 20 mg, and 30 mg of adefovir dipivoxil. Peak plasma concentrations (C(max)) were (26.6 +/- 6.1), (55.7 +/- 16.2), and (70.2 +/- 11.8) ng/mL, respectively; time to C(max) (T(max)) were (1.5 +/- 0.6), (1.6 +/- 0.7), and (1.8 +/- 0.6) h, respectively; the area under the plasma concentration versus time curve from time 0 h to 36 h (AUC(0-36)) were (184.5 +/- 25.2), (379.3 +/- 61.8) and (556.5 +/- 86.7) ng/mL, respectively; mean residence times (MRT) were (8.9 +/- 0.9), (9.0 +/- 1.0), and (8.9 +/- 1.0) h, respectively; and the elimination half-life (t(1/2)) were (8.0 +/- 0.9), (7.5 +/- 0.8), and (7.5 +/- 0.9) h, respectively. The pharmacokinetic parameters can provide some information for clinical medication.
已开发出一种选择性和灵敏的高效液相色谱 - 电喷雾串联质谱法（HPLC - ESI - MS - MS），以腺嘌呤（PMPA）为内标物测定人血浆中的阿德福韦。用甲醇进行蛋白沉淀后，血浆样品在反相XTerra MS/MS C(18)柱（100 mm×2.1 mm内径，3.5 mm）上通过HPLC分离，流动相为甲醇 - 水（20:80，v/v）。标准曲线在0.20 - 100 ng/mL浓度范围内呈线性（r(2)=0.9962），且具有可接受的准确度和精密度。批内和批间精密度均在11.30%以内。定量下限（LLOQ）为0.20 ng/mL。经过验证的HPLC - ESI - MS - MS方法已成功用于研究阿德福韦在健康中国志愿者中的药代动力学。在给予10 mg、20 mg和30 mg阿德福韦酯单剂量后，阐明了以下药代动力学参数。血浆峰浓度（C(max)）分别为(26.6±6.1)、(55.7±16.2)和(70.2±11.8) ng/mL；达峰时间（T(max)）分别为(1.5±0.6)、(1.6±0.7)和(1.8±0.6) h；从0 h到36 h的血浆浓度 - 时间曲线下面积（AUC(0 - 36)）分别为(184.5±25.2)、(379.3±61.8)和(556.5±86.7) ng/mL；平均驻留时间（MRT）分别为(8.9±0.9)、(9.0±1.0)和(8.9±1.0) h；消除半衰期（t(1/2)）分别为(8.0±0.9)、(7.5±0.8)和(7.5±0.9) h。这些药代动力学参数可为临床用药提供一些信息。
