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目的建立盐酸美沙酮(MTD)人体内血药浓度的测定方法 ,并对口服MTD口服液后的美沙酮维持治疗患者(MMTPs)体内的药动学过程进行研究。方法采用Agilent ZORBAX SB-C_(18)(250mm×4.6 mm,5μm)色谱柱,以乙腈-磷酸盐缓冲液(pH 2.5)=32:68(V/V)为流动相,流速1.50 mL·min~(-1),检测波长206 nm,盐酸苯海索为内标,对血浆中的MTD浓度进行检测。8名MMTPs口服MTD口服液80 mg,分别于服药前和服药后1、2、3、4、6、8、12、24 h采集血样,测定血浆中MTD的浓度,并采用3P97药动学软件对试验数据进行处理,计算有关药动学参数。结果在0.10～10.00 mg·L~(-1)内,MTD与内标峰面积的比值与浓度之间呈良好的线性关系(r=0.999 6)。日内及日间精密度(RSD)和回收率均符合要求。MTD药-时曲线经拟合符合二室模型,主要参数:ρ_(max)(623.13 4-231.06)μg·L~(-1);t_(max)为(2.764±1.13)h;AUC_(0→24h)为(9 569.56±3 294.88)μg·h·L~(-1);AUC_(0→∞)为(21 522.61±10 825.36)μg·h·L~*(-1);t_(1/2)为(23.95±13.61)h。结论本试验建立的检测人血浆中MTD含量的HPLC法,适用性强,重复性好,操作简单,快速准确,成本低廉,可用于MTD药动学的研究;MTD药动学特征和参数在个体间存在较大差异,临床治疗中应实施个体化治疗方案。
Objective To establish a method for the determination of human plasma concentration of methadone hydrochloride (MTD) in human and to study the pharmacokinetics of methadone maintenance treatment (MMTPs) in oral MTD oral solution. Methods The mobile phase consisted of Agilent ZORBAX SB-C 18 column (250 mm × 4.6 mm, 5 μm) and acetonitrile-phosphate buffer (pH 2.5) = 32:68 (V / V) at a flow rate of 1.50 mL · min ~ (-1), the detection wavelength was 206 nm, and the content of MTD in plasma was detected by the internal standard. 8 MMTPs orally taken oral MTD 80 mg, respectively, before taking the medicine and taking 1,2,3,4,6,8,12,24 h after taking blood samples, determination of plasma concentrations of MTD and the use of 3P97 pharmacokinetics software The experimental data processing, calculation of the pharmacokinetic parameters. The results showed that there was a good linear relationship between the concentration of MTD and internal standard peak area (r = 0.999 6) within the range of 0.10-10.00 mg · L -1. Intra-day and inter-day precision (RSD) and recovery rates were met. MTD drug-time curve fitting fitted two-compartment model, the main parameters: ρ_ (max) (623.13 4-231.06) μg · L -1; t max; 2.764 ± 1.13 h; AUC_0 → 24 h) was (9 569.56 ± 3 294.88) μg · h · L -1, and AUC 0 ~ ∞ was 21 522.61 ± 10 825.36 μg · h · L -1 * 1/2) was (23.95 ± 13.61) h. Conclusion The established HPLC method for the determination of MTD in human plasma has strong applicability, good repeatability, simple operation, fast and accurate, low cost and can be used for the study of MTD pharmacokinetics. MTD pharmacokinetic characteristics and parameters in individuals There is a big difference between the clinical treatment should be implemented in individual treatment programs.