Wheeler L A, De Meo M, Halula M, George L, Heseltine P
Antimicrob Agents Chemother. 1978 Feb;13(2):205-9. doi: 10.1128/AAC.13.2.205.
A rapid and sensitive high-pressure liquid chromatography assay for metronidazole and its two principle metabolites, 1-(2-hydroxyethyl-2-hydroxymethyl)-5-nitro-imidazole [hydroxy metabolite] and 1-acetic acid-2-methyl-5-metronidazole [acid metabolite], was developed. The retention times observed were 5.7, 3.3, and 4.5 min, respectively. A reverse-phase muC(18) Bondapak column using a solvent system of methanol, acetonitrile, and 0.005 M pH 4 potassium dihydrogen phosphate (4:3:93, vol/vol) was used to achieve separation of the three compounds. Patients receiving metronidazole therapy were given a loading dose of 13.6 mg of drug per kg intravenously over 1 h, followed by a maintenance dose of 1.43 mg/kg per h. The range of metronidazole concentrations observed was 6.8 to 47.5 mug/ml. These levels are well above the minimal inhibitory concentrations of most clinically significant anaerobic bacteria including Bacteroides fragilis. Little of the acid metabolite was observed in the plasma. The concentration of hydroxy metabolite ranged from 1.6 to 16 mug/ml. The latter may represent an additional source of antimicrobial activity since the hydroxy metabolite has approximately 30% the biological activity of metronidazole.
开发了一种快速灵敏的高压液相色谱法，用于测定甲硝唑及其两种主要代谢物，即1-(2-羟乙基-2-羟甲基)-5-硝基咪唑[羟基代谢物]和1-乙酸-2-甲基-5-甲硝唑[酸代谢物]。观察到的保留时间分别为5.7、3.3和4.5分钟。使用反相μC(18) Bondapak柱，以甲醇、乙腈和0.005 M pH 4磷酸二氢钾(4:3:93，体积/体积)的溶剂系统实现这三种化合物的分离。接受甲硝唑治疗的患者先静脉注射负荷剂量的药物，每千克13.6毫克，持续1小时，随后是维持剂量，每小时1.43毫克/千克。观察到的甲硝唑浓度范围为6.8至47.5微克/毫升。这些水平远高于包括脆弱拟杆菌在内的大多数临床重要厌氧菌的最低抑菌浓度。在血浆中观察到的酸代谢物很少。羟基代谢物的浓度范围为1.6至16微克/毫升。后者可能代表抗菌活性的另一个来源，因为羟基代谢物的生物活性约为甲硝唑的30%。
