反相高效液相色谱法有效分离和同时测定人体尿液中7种喹诺酮

目的 建立一种同时检测人体尿液中吡哌酸与依诺沙星、氟罗沙星、培氟沙星、洛美沙星、环丙沙星和恩氟沙星7种氟喹诺酮类药物的反相高效液相色谱法.方法 色谱柱为ZY1104型C18色谱柱(250 mm×4.6mm,5μm),柱温30℃.流动相为乙腈0.02mol/L四丁基溴化铵(体积比为991).以三氟乙酸缓冲液调pH 2.87,流速1.0ral/min.检测波长282nm,进样量20μl.结果 7种药物的校准曲线在0.5～100μg/ml浓度范围内呈良好的线性,相关系数r≥0.9996,检出限为0.036～0.088ttg/ml.样品的平均加标回收率在91.6%～99.5%,RSD＜7%(n=5).结论 所提出的方法简便,快速,可靠,能有效分离和同时测定人体尿液中的多种喹诺酮.     

吡哌酸的电化学行为研究及其单扫示波极谱测定

吡哌酸在ｐＨ４．５,０．２ｍｏｌ／Ｌ的醋酸盐缓冲溶液中有灵敏的单扫极谱吸附波。在６×１０－８～２×１０－６ｍｏｌ／Ｌ范围内吡哌酸的浓度与其波高成直线关系,检测下限２×１０－８ｍｏｌ／Ｌ。利用该波测定了吡哌酸片中吡哌酸的含量,结果满意。吡哌酸在该溶液中的汞电极上的吸附服从Ｌａｎｇｍｕｉｒ等温线,吸附系数β＝５．４×１０５;电极反应的电子传递系数α＝０．６８,表面电极反应速率常数ｋｓ＝０．６８ｓ－１。     

紫外分光光度法测定吡哌酸片含量的不确定度评定

目的：建立紫外分光光度法（UV）测定吡哌酸片含量的不确定度评定方法。方法：通过数学模型,对各个不确定度分量进行评定。结果：计算出了测定结果的扩展不确定度和置信水平。结论：建立的方法为同类实验提供了有益的参考。     

Micellar electrokinetic chromatography for determination of drug partition in phospholipids

The lipophilicity of pipemidic, nalidixic and oxolinic acids was determined by forming phospholipidic micelles directly in an electrophoretic capillary. Phosphatidylcholine derivatives, namely L-alpha-dilauroyl phosphatidylcholine (DLPC) or L-alpha-dimiristoyl phosphatidylcholine (DMPC), were added in the run buffer (50 mM phosphate buffer at pH 7.4). To obtain a mixed micelle, phospholipidic derivatives and sodium cholate were together added in the run buffer. Considering the increasing of migration time when phosphatidylcholine derivative is added in the run buffer, Ks can be determined and then quinolones lipophilicity.     

柿霜吡哌酸粉双层缓释口腔贴膜的制备及评价

目的制备柿霜吡哌酸（PPA）粉双层缓释口腔贴膜,并对其进行质量评价。方法评价贴膜的膜外观、体外黏附力、溶解时间和口腔黏附时间,测定贴膜中PPA含量及贴膜的体外释放度,评价其体外释药行为。结果口腔贴膜的体外黏附力为137 g/cm2,溶解时间为22.74 min,口腔黏附时间为23.59 min。含量测定结果显示,PPA量在0.18~0.54 mg/mL之间有良好的线性关系（r=0.9965）,回收率为100.54%,RSD=0.78%（n=6）。体外释药行为符合一级动力学方程。结论柿霜PPA粉双层缓释口腔贴膜处方及制备工艺合理可行,质量符合要求。     

The influence of magnesium stearate on the characteristics of mucoadhesive microspheres

Microspheres containing the mucoadhesive polymer chitosan hydrochloride, with matrix polymer Eudragit RS, pipemidic acid as a model drug and agglomeration preventing agent magnesium stearate were prepared by the solvent evaporation method. The amount of magnesium stearate was varied and the following methods were used for microsphere evaluation: sieve analysis, drug content and dissolution determination, scanning electron microscopy, xray diffractometry, DSC and FTIR spectroscopy. The results showed that average particle size decreased with increasing amount of magnesium stearate used for microsphere preparation. This is probably a consequence of stabilization of the emulsion droplets with magnesium stearate. Higher pipemidic acid content in the microspheres was observed in larger particle size fractions and when higher amounts of magnesium stearate were used. It was also found that these two parameters significantly influenced the dissolution rate. The important reason for the differences in drug content in microspheres of different particle sizes is the diffusion of pipemidic acid from the acetone droplets in liquid paraffin during the preparation procedure. The physical state of pipemidic acid changed from crystalline to mostly amorphous with its incorporation in microspheres, as shown by x-ray diffractometry and differential     

Pharmacokinetic determination of relative potency of quinolone inhibition of caffeine disposition

Summary Quinolone is reported to interact with caffeine, often resulting in an increase both in the plasma half-life and AUC, a decrease in total plasma clearance, and little change in the absorption rate constant and maximum plasma level. These complex changes in the pharmacokinetics of caffeine were analyzed experimentally and from published reports in order to determine the nature of the interaction, which is thought to be due to inhibition of caffeine metabolism by quinolones. A simple pharmacokinetic model for the caffeine-quinolone interaction was developed, which provides a unified method for evaluation and comparison of the effect of quinolones on the disposition of caffeine. The model is applicable to other methylxanthines, such as theophylline. The relative potency of the interactions of quinolones with caffeine in humans has been established as enoxacin (100), pipemidic acid (29), ciprofloxacin (11), norfloxacin (9) and ofloxacin (0).     

三种国产喹诺酮类药物对高接种量志贺氏菌的抗菌活性

测试了吡哌酸、氟哌酸和环丙氟哌酸等三种国产喹诺酮类药物对60株志贺氏菌高接种量(10~7CFU/ml)和标准接种量(10~5CFU/ml)的抗菌活性。结果表明,高接种量与标准接种量相比,药物最小抑菌浓度(MIC)增大16～256倍,氨苄青霉素和庆大霉素高接种量与标准接种量相比,MIC仅增高2倍。氨苄青霉素是对其敏感的志贺氏菌所致的重型菌痢较好的首选药物。而喹诺酮类药物如使用不当,不仅不能杀死志贺氏菌,反而诱导选择出耐药菌,给治疗带来新问题。     

Microfluidic-enzymatic biosensor with immobilized tyrosinase for electrochemical detection of pipemidic acid in pharmaceutical samples

The present article describes the development of a microfluidic-enzymatic sensor with electrochemical detection for the quantification of pipemidic acid (PA), which is a synthetic quinolone used as antibacterial agent. This property of the quinolones is associated with their potential to inhibit topoisomerase II (DNA gyrase) of bacteria. PA detection in pharmaceutical samples was based in the use of tyrosinase enzyme [EC 1.14.18.1] that was immobilized on 3-aminopropyl-modified-controlled-pore glass (APCPG) packet in a central channel (CC) of the microfluidic-enzymatic device. This enzyme catalyzes the oxidation of catechol to o-benzoquinone, whose back electrochemical reduction was detected at gold electrode surface at 0 V vs. Ag/AgCl. Thus, when PA was added to the solution, this piperazine-containing compound participates in a Michael addition reaction with o-benzoquinone to form the corresponding amino-quinone derivative, as result of this interaction the peak current obtained for o-benzoquinone reduction decreased proportionally to the increase of the PA concentration. The recovery of PA from four samples ranged from 97.50% to 102.50%. This method could be used to determine the PA concentration in the range 0.02–70 μM (r = 0.998) with a limit of detection of 18 nM. This method was successfully applied for the analysis of PA in pharmaceutical formulations.     

吡哌酸(Pipemidic Acid)的合成

呲哌酸为一合成抗菌剂,对革兰氏阴性杆菌、绿脓杆菌都有较强的抗菌作用,临床上常用于全身性感染及各种泌尿系统感染的疾病,本文列举了目前所采用的尿素路线所存在的严重问题,并详细介绍了甲基异硫脲路线的特点及其工艺过程。本路线的总收率可达44.27%。