Mihaly G W, Cockbain S, Jones D B, Hanson R G, Smallwood R A
J Pharm Sci. 1982 May;71(5):590-2. doi: 10.1002/jps.2600710528.
An assay is described for the determination of the H2-receptor antagonist, cimetidine, in human plasma and urine. Alkalinized plasma or urine was extracted with methylene chloride, the organic phase was evaporated, and the reconstituted residue was analysed by high-pressure liquid chromatography (HPLC) using a reversed-phase prepacked plastic column housed in a radial compression module. The metabolite, cimetidine sulfoxide, was identified but could not be quantitated due to interference from the solvent front. The sensitivity limit of the assay was 25 ng/ml. The assay was applied to the measurement of plasma and urine samples in a pilot pharmacokinetic study. Cimetidine was substantially absorbed and rapidly eliminated (plasma elimination half-life of 112-130 min). Plasma cimetidine concentrations could be measured to 12 hr after a 200-mg dose (iv or oral), but they were below the sensitivity of the assay by 24 hr. Urinary excretion of unmetabolized cimetidine accounted for 40-50% of the administered dose in the first 12 hr. This assay is simpler and more sensitive than those previously described, and it is suitable for the measurement of cimetidine in plasma and urine of subjects receiving doses appropriate for clinical use.
本文描述了一种用于测定人血浆和尿液中H2受体拮抗剂西咪替丁的分析方法。将碱化后的血浆或尿液用二氯甲烷萃取，有机相蒸发后，用装在径向压缩模块中的反相预填充塑料柱通过高压液相色谱（HPLC）对重构后的残渣进行分析。已鉴定出代谢物西咪替丁亚砜，但由于溶剂前沿的干扰无法进行定量。该分析方法的灵敏度极限为25 ng/ml。在一项初步药代动力学研究中，该方法被用于测量血浆和尿液样本。西咪替丁吸收良好且消除迅速（血浆消除半衰期为112 - 130分钟）。静脉注射或口服200 mg剂量后，可在12小时内测定血浆中西咪替丁浓度，但在24小时时低于该分析方法的灵敏度。在最初12小时内，未代谢的西咪替丁经尿液排泄量占给药剂量的40 - 50%。该分析方法比之前描述的方法更简单、更灵敏，适用于测量接受临床适用剂量的受试者血浆和尿液中的西咪替丁。
