Kusajima H, Ooie T, Kawahara F, Uchida H
J Chromatogr. 1986 Aug 22;381(1):137-48. doi: 10.1016/s0378-4347(00)83572-0.
A simple, sensitive and specific high-performance liquid chromatographic method for a new quinolone antimicrobial agent, 6,8-difluoro-1-(2-fluoroethyl)-1,4- dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid (AM-833, I), and its metabolites in serum and urine has been developed for their simultaneous determination. This method is based on ion-pair extraction and separation by ion-pair reversed-phase chromatography with ultraviolet or fluorescence detection. The major metabolites in the serum and urine of mice, rats, dogs and monkeys were N-desmethyl I (compound II) and I N-oxide (compound III). Rabbit serum and urine contained N-desmethyl-3-oxo I (compound IV), 3-oxo I (compound V) and N-desmethyl-4-formyl I (compound VI) in addition to compounds I, II and III. Unchanged drug accounted for 80-90% of total serum concentrations in mice and more than 90% in rats, dogs and monkeys up to 6 h after dosing, whereas the fraction of compound I in rabbits was 34-67%. Unchanged drug was the most predominant in the urine of mice, rats, dogs and monkeys, whereas compound II was the most abundant in rabbit urine. Although rabbits and monkeys excreted 70-80% of dose in three-day urine, the total urinary excretion of mice, rats and dogs was relatively low, 40-50% of oral dose. The fraction of compound I in total urinary excretion was 63, 73, 27, 55 and 78% in mice, rats, rabbits, dogs and monkeys, respectively. These results suggest that there is a species difference in the metabolism and excretion pathway of compound I.
已开发出一种简单、灵敏且特异的高效液相色谱法，用于同时测定一种新型喹诺酮抗菌剂6,8 - 二氟 - 1 - (2 - 氟乙基)-1,4 - 二氢 - 7 - (4 - 甲基 - 1 - 哌嗪基)-4 - 氧代 - 3 - 喹啉羧酸（AM - 833，I）及其在血清和尿液中的代谢产物。该方法基于离子对萃取，并通过离子对反相色谱结合紫外或荧光检测进行分离。小鼠、大鼠、狗和猴血清及尿液中的主要代谢产物为N - 去甲基I（化合物II）和I N - 氧化物（化合物III）。兔血清和尿液中除化合物I、II和III外，还含有N - 去甲基 - 3 - 氧代I（化合物IV）、3 - 氧代I（化合物V）和N - 去甲基 - 4 - 甲酰基I（化合物VI）。给药后6小时内，小鼠血清中未变化的药物占总血清浓度的80 - 90%，大鼠、狗和猴中则超过90%，而兔中化合物I的比例为34 - 67%。未变化的药物在小鼠、大鼠、狗和猴的尿液中占比最大，而化合物II在兔尿液中含量最高。尽管兔和猴在三天尿液中排泄了70 - 80%的剂量，但小鼠、大鼠和狗的总尿排泄量相对较低，为口服剂量的40 - 50%。化合物I在小鼠、大鼠、兔、狗和猴的总尿排泄量中的比例分别为63%、73%、27%、55%和78%。这些结果表明化合物I的代谢和排泄途径存在种属差异。
