Watson D G, Araya F G, Galloway P J, Beattie T J
Department of Pharmaceutical Sciences, Strathclyde Institute of Biomedical Science (SIBS), University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, UK.
J Pharm Biomed Anal. 2004 Apr 1;35(1):87-92. doi: 10.1016/j.jpba.2003.12.011.
In order to facilitate the simultaneous determination of the levels of mycophenolic acid (MPA) and mycophenolic acid glucuronide (MPAG) in plasma samples a step wise gradient high performance liquid chromatography (HPLC) method was developed using UV detection system and naproxen as an internal standard. The analytes were extracted from plasma using Strata-X polymeric solid phase extraction (SPE) cartridges. Separation was achieved within a total chromatographic run time of 18 min at 1.0 ml/min flow rate using a Hv PURITY C18 column. The method was found to be linear over the concentration range investigated, 1.0-16 microg/ml (r > 0.99) for MPA and 10-160 microg/ml (r > 0.99) for MPAG. The limit of detection was 0.1 microg/ml for both MPAG and MPA. The intra- and inter-day imprecisions expressed as R.S.D. were 7.8 and 6.6%, respectively, for MPA (1 microg/ml) and 6.2% and 5.6%, respectively, for MPAG (20 microg/ml). The average extraction recovery from plasma was 93.06%, for MPA and 92.41% for MPAG. The method developed was found to be accurate and precise in quantifying the level of MPA and MPAG over a their therapeutic range of concentrations in small volumes of plasma and thus can be effectively used in the routine drug monitoring procedures and pharmacokinetic studies. It was also developed in such a way that it should be easily coupled to an electro-spray ionization mass spectrometer should greater sensitivity be required.
为便于同时测定血浆样本中霉酚酸（MPA）和霉酚酸葡萄糖醛酸苷（MPAG）的水平，开发了一种采用紫外检测系统并以萘普生作为内标的梯度高效液相色谱（HPLC）方法。使用Strata-X聚合物固相萃取（SPE）柱从血浆中提取分析物。采用Hv PURITY C18柱，在流速为1.0 ml/min的条件下，总色谱运行时间18分钟内实现分离。该方法在所研究的浓度范围内呈线性，MPA为1.0 - 16 μg/ml（r > 0.99），MPAG为10 - 160 μg/ml（r > 0.99）。MPAG和MPA的检测限均为0.1 μg/ml。以相对标准偏差（R.S.D.）表示的日内和日间不精密度，MPA（1 μg/ml）分别为7.8%和6.6%，MPAG（20 μg/ml）分别为6.2%和5.6%。血浆中MPA的平均提取回收率为93.06%，MPAG为92.41%。所开发的方法在小体积血浆中MPA和MPAG的治疗浓度范围内定量测定其水平时准确且精密，因此可有效用于常规药物监测程序和药代动力学研究。该方法的开发方式使其在需要更高灵敏度时可轻松与电喷雾电离质谱仪联用。
