Moncrieff J
Department of Pharmacology, Faculty of Medicine, University of Pretoria, South Africa.
J Chromatogr. 1991 Jul 17;568(1):177-85. doi: 10.1016/0378-4347(91)80351-c.
Because of marked variability in its metabolic clearance and its narrow therapeutic range (10-20 micrograms/ml) investigation of each patient's clearance of theophylline is desirable. The author reports here a rapid reversed-phase high-performance liquid chromatographic (HPLC) method to determine, within 3 min, the theophylline in serum and saliva in the 0.1-50 micrograms/ml range. A fast HPLC column, 10 x 4.6 mm, packed with 3-microns spherical ODS packing is used with acetonitrile-methanol-buffer pH 4.7 (4:7:89) to achieve separation of theophylline from paraxanthine and matrix components. Since theophylline is a major pediatric bronchodilator, the feasibility of assay in saliva was investigated as an alternative route for determining the clearance is stressed asthmatic children. Using this method it was found that the ratio of theophylline in simultaneous serum and saliva samples is very consistent over time in the same person (+/- 3.99%), but inter-individually this consistency is reduced ten-fold. Simultaneous serum and saliva samples need be taken only once to obtain the ratio and the kinetics followed further with salivary samples only.
由于其代谢清除率存在显著差异且治疗范围狭窄(10 - 20微克/毫升),因此对每位患者的茶碱清除率进行研究是很有必要的。作者在此报告了一种快速反相高效液相色谱(HPLC)方法,可在3分钟内测定血清和唾液中浓度范围为0.1 - 50微克/毫升的茶碱。使用一根10×4.6毫米的快速HPLC柱,填充3微米球形ODS填料,以乙腈 - 甲醇 - pH 4.7缓冲液(4:7:89)实现茶碱与副黄嘌呤及基质成分的分离。由于茶碱是主要的儿科支气管扩张剂,本文研究了唾液检测的可行性,以此作为测定哮喘儿童清除率的另一种途径。使用该方法发现,同一人同时采集的血清和唾液样本中茶碱的比例随时间推移非常一致(±3.99%),但个体间这种一致性降低了十倍。同时采集血清和唾液样本只需一次以获取比例,后续仅用唾液样本跟踪动力学情况。