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目的建立液相色谱-串联质谱(LC-MS/MS)法测定人血浆中右溴苯那敏的浓度,并评价右溴苯那敏在健康受试者体内的药动学特征。方法血浆经参有氯苯那敏为内标的甲醇沉淀后在Inertsil ODS-3柱(150 mm×2.1 mm,5μm)上分离,流动相采用含10 mmol·L~(-1)甲酸铵的甲醇/水/甲酸(60∶40∶0.1,V/V/V)溶液。串联质谱Sciex API 3000采用正电喷雾离子源和多反应监测的扫描模式。结果右溴苯那敏在0.1～40μg·L~(-1)内线性良好,定量下限为0.1μg·L~(-1)。方法的准确度为87%～113%,批内、批间的RSD均<15%。右溴苯那敏的主要药动学参数ρ_(max)、t_(max)、t_(1/2)、AUC_(0→t)和AUC_(0→∞)在单剂量给药后分别为:(3.58±1.14)μg·L~(-1)、(9.42±2.94)h、(18.46±9.48)h、(108.4±53.97)μg·h·L~(-1)和(126.3±73.91)μg·h·L~(-1);在多剂量给药后分别为:(14.59±6.75)μg·L~(-1),(6.35±2.09)h、(21.40±7.74)h、(487.9±316.2)μg·h·L~(-1)和(578.0±437.3)μg·h·L~(-1)。稳态时的药动学参数AUC~(ss)、ρ_(min)、ρ_(av)和DF分别为:(153.0±74.47)μg·h·L~(-1)、(12.07±5.84)μg·L~(-1)、(12.75±6.21)μg·L~(-1)和(21.2±7.7)%。结论本方法专属性强,精确,灵敏度高,操作简单,快速。结果表明单剂量和多剂量给药后ρ_(max)、t_(max)和AUC_(0→t)之间的差异有统计学意义,右溴苯那敏在体内有蓄积。
Objective To establish a liquid chromatography-tandem mass spectrometry (LC-MS / MS) method for the determination of dexbromethazine in human plasma and to evaluate the pharmacokinetics of dexbromine in healthy volunteers. Methods The plasma was separated on a Inertsil ODS-3 column (150 mm × 2.1 mm, 5 μm) after precipitation with chlorpheniramine as the internal standard. The mobile phase consisted of methanol containing 10 mmol·L -1 ammonium formate / Water / formic acid (60:40: 0.1, V / V / V) solution. Tandem mass spectrometry The Sciex API 3000 employs positive-ion spray ionization and multi-reaction monitoring scan modes. Results dexbrompheniramine was linear in the range of 0.1-40 μg · L -1 with a lower limit of quantitation of 0.1 μg · L -1. The accuracy of the method was 87% -113%, with an RSD of <15% between batches and batches. The main pharmacokinetic parameters ρ max, t max, t 1/2, AUC 0 - t and AUC 0 - ∞ of dexbromiben were respectively: (3.58 ± 1.14) μg · L -1, (9.42 ± 2.94) h, (18.46 ± 9.48) h, (108.4 ± 53.97) μg · h · L -1 and (126.3 ± 73.91) μg · H · L ~ (-1), respectively; (14.59 ± 6.75) μg · L -1, (6.35 ± 2.09) h, (21.40 ± 7.74) h, (487.9 ± 316.2) μg · h · L ~ (-1) and (578.0 ± 437.3) μg · h · L ~ (-1) respectively. The pharmacokinetic parameters AUC, ρ min, ρ av and DF at steady state were 153.0 ± 74.47 μg · h · L -1 and 12.07 ± 5.84 μg respectively · L -1, (12.75 ± 6.21) μg · L -1 and (21.2 ± 7.7)% respectively. Conclusion This method is highly specific, accurate, sensitive, easy to operate and fast. The results showed that there was a significant difference between ρ max, t max and AUC 0 0 t after single-dose and multi-dose administration, and dexbromine was accumulated in vivo.