Liao Qiongfeng, Deng Yating, Xie Zhiyong, Pan Biyan, Zhang Lei
College of Chinese Traditional Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
J Sep Sci. 2009 Jan;32(2):202-11. doi: 10.1002/jssc.200800417.
A rapid and sensitive high-performance LC-MS/MS method was developed and validated for the simultaneous quantification of codeine and its metabolite morphine in human plasma using donepezil as an internal standard (IS). Following a single liquid-liquid extraction with ethyl acetate, the analytes were separated using an isocratic mobile phase on a C(18 )column and analyzed by MS/MS in the selected reaction monitoring mode using the respective M+Hions, mass-to-charge ratio (m/z) 300/165 for codeine, m/z 286/165 for morphine and m/z 380/91 for IS. The method exhibited a linear dynamic range of 0.2-100/0.5-250 ng/mL for codeine/morphine in human plasma, respectively. The lower LOQs were 0.2 and 0.5 ng/mL for codeine and its metabolite morphine using 0.5 mL of human plasma. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. A run time of 2.0 min for each sample made it possible to analyze more than 300 human plasma samples per day. The validated LC-MS/MS method was applied to a pharmacokinetic study in which healthy Chinese volunteers each received a single oral dose of 30 mg codeine phosphate.
建立了一种快速、灵敏的高效液相色谱-串联质谱法，并进行了验证，用于以多奈哌齐为内标（IS）同时定量人血浆中的可待因及其代谢产物吗啡。用乙酸乙酯进行单次液-液萃取后，在C(18)柱上使用等度流动相分离分析物，并在选择反应监测模式下通过串联质谱进行分析，分别使用各自的M+H离子，可待因的质荷比（m/z）为300/165，吗啡的m/z为286/165，内标的m/z为380/91。该方法在人血浆中可待因/吗啡的线性动态范围分别为0.2 - 100/0.5 - 250 ng/mL。使用0.5 mL人血浆时，可待因及其代谢产物吗啡的最低定量限分别为0.2和0.5 ng/mL。在标准曲线范围内的浓度获得了可接受的精密度和准确度。每个样品的运行时间为2.0分钟，使得每天能够分析300多个人类血浆样品。经过验证的液相色谱-串联质谱法应用于一项药代动力学研究，其中健康中国志愿者每人单次口服30 mg磷酸可待因。
