氯霉素乳膏的制备及质量标准的研究

目的制备氯霉素乳膏并制订质量控制方法。方法以生物测定法检测氯霉素的含量。结果在30.13~79.91u·mL-1浓度范围内的剂量对数与抑菌圈直径呈良好线性关系,r=0.9996。结论该制剂的制备工艺简便,质量稳定。     

HPLC法测定复方氯霉素醇溶液中氯霉素的含量

目的研究复方氯霉素醇溶液中氯霉素含量的HPLC测定法。方法色谱柱：ZORBAX 80A Extend-C18,紫外检测器波长：278nm,流速：1mL·min^-1。流动相组成：0.1%庚烷磺酸钠溶液（取0.1%的庚烷磺酸钠500mL与二甲基甲酰胺5mL、冰醋酸0.5mL,混匀）-乙腈（75∶25）。结果氯霉素浓度在9.96～99.64μg·mL^-1范围内与峰面积具有良好的线性关系（r=0.99989）,平均回收率为100.85%（RSD=0.50%）。结论本方法测定氯霉素具有简便、准确的特点。     

HPLC法测定制霉菌素氯霉素栓中氯霉素的含量

目的：建立HPLC法测定制霉菌素氯霉素栓中氯霉素的含量。方法：色谱柱为Agilent XDB-C18（4.6mm×250mm,5μm）;流动相为0.01mol/L庚烷磺酸钠缓冲溶液（pH2.5）∶甲醇（68∶32）;流速1.0ml·min-1;检测波长为277nm。结果：氯霉素在2.467～49.340μg·ml^-1浓度范围内线性关系良好,r=0.9999,平均回收率为99.82%,RSD为0.4%（n=9）。结论：此法简单可行,准确可靠,可用于制霉菌素氯霉素栓中氯霉素的含量测定。     

RP-HPLC测定氯霉素耳栓的含量

采用RP-HPLC法测定氯霉素耳栓中氯霉素的含量。用C18色谱柱,以甲醇∶乙腈∶0.8%冰乙酸溶液(12∶25∶63)为流动相,检测波长278nm。氯霉素的线性方程C=2.57×1-0 6A-7.72×10-4,r=0.9999;范围为10~120μg/m l;回收率为99.8%,RSD=0.65%。该方法操作简单,灵敏度高,定量准确。     

改进高效液相色谱法测定氯霉素滴耳液及其相关物质二醇物的含量

目的建立以改进的高效液相色谱法（HPLC）分离测定氯霉素滴耳液的含量,并对其中降解产物二醇物进行控制。方法固定相为KromasilC18色谱柱（4.6mm×250mm,5μm）,流动相为甲醇-乙腈-0.15%磷酸（1∶3∶5）;流速为1.0ml/min,柱温：35℃,检测波长为270nm。结果氯霉素的平均回收率为99.61%,RSD为0.46%。氯霉素二醇物的平均回收率为99.41%,RSD为0.77%。结论该法可同时测定氯霉素滴耳液中氯霉素与氯霉素二醇物的含量,而且快速、准确、简便、灵敏度高、分离度好。     

高效液相色谱法测定复方氯霉素滴眼液中氯霉素的含量

目的 :建立测定复方制剂中氯霉素含量的方法。方法 :采用反相HPLC法 ,以C18为固定相 ,甲醇 水 (1∶1)为流动相 ,检测波长 :2 78nm。结果 :氯霉素在 2 6 .6～ 16 0 .2 μg·ml-1浓度范围内具有良好的线性关系。平均回收率为 10 0 .1%。结论 :本方法简便 ,可靠 ,与其他成分分离效果好 ,可有效测定该复方制剂中氯霉素的含量。     

高效液相色谱法测定氯霉素注射液中氯霉素的含量

目的 建立一种准确度和灵敏度高,重现性好的氯霉素注射液中氯霉素含量测定的高效液相色谱法.方法 采用shim pack VP ODS(150mm*4.6mm,5μm)为分析柱,流动相0.1%庚烷磺酸钠溶液(取0.1%庚烷磺酸钠500mL与二甲基甲酰胺5mL,冰醋酸0.5mL,混匀)∶乙腈(75∶25),检测波长:272nm,流速:1.0mL·min-1.结果 氯霉素在0.040～0.200 mg内有良好的线性关系,回收率为99.8%,RSD为0.80%.结论 建立的氯霉素含量测定方法简便,准确,灵敏.     

HPLC法测定氯霉素地塞米松乳膏中氯霉素的含量

目的:建立氯霉素地塞米松乳膏的含量测定方法.方法:采用高效液相色谱法:色谱条件为:Kromasil C18柱(250×4.6mm,5μm);流动相:0.01mol/L庚烷磺酸钠缓冲溶液-甲醇(65:35);检测波长:277nm;流速:1.00rL/min.结果:氯霉素进样量在0.4016～8.032μg范围内,呈良好的线性关系,r=0.9999.平均加样回收率为98.3％,RSD为0.53％.结论:该方法简便快速,准确,重现性好.可有效控制氯霉素地塞米松乳膏中氯霉素的含量.     

Microdialysis study of biliary excretion of chloramphenicol and its glucuronide in the rat.

The biliary excretion of chloramphenicol and its glucuronide has been evaluated by use of a microdialysis probe linked to automatic on-line microbore high-performance liquid chromatography. The microdialysis probe was inserted into the bile duct between the liver and the duodenum; to avoid obstruction of the bile duct or bile salt waste, a shunt linear probe was used. After intravenous administration of chloramphenicol succinate (100 mg kg(-1)) the amounts of unbound chloramphenicol and its glucuronide in the bile microdialysate were recorded. According to the pharmacokinetic results disposition of chloramphenicol seems to fit a two-compartment model whereas that of chloramphenicol glucuronide fits a one-compartment model in rat bile. The area under the concentration-time curve for chloramphenicol glucuronide was twice that for chloramphenicol in rat bile duct. Clearance of chloramphenicol glucuronide was significantly higher than that of chloramphenicol in biliary excretion, indicating that chloramphenicol and its glucuronide are actively excreted into the bile.     

紫外分光光度法测定氯霉素滴眼液的含量

目的：测定氯霉素滴眼液的含量。方法：以空白基质溶液为参照液，应用紫外分光光度法，测定波长280nm，消除了处方中羟苯乙酯等成分对测定结果的干扰。结果：平均回收率101.36％，RSD为0.95％。结论：该法简单，快捷，适合医院快速检验。     

Chloramphenicol dosage and pharmacokinetics in infants and children

Twenty infants and children receiving intravenous chloramphenicol were studied to examine the pharmacokinetics of the parent compound and its precursor, the succinate ester (CAP-S). Plasma samples were obtained just prior to a 30-minute infusion of chloramphenicol succinate, immediately after or 30 minutes after infusion, and 90, 210, and 330 minutes after infusion. Complete 6-hour urine collections were obtained during 11 studies. Plasma and urine were assayed for chloramphenicol and its succinate ester by high-performance liquid chromatography. Peak plasma concentrations ranged from 11.0 to 51.1 micrograms/ml on doses of 50 to 100 mg/kg/day and were higher in the youngest age group. The elimination half-life of chloramphenicol averaged 4.0 hours. Multilinear regression analysis demonstrated an excellent relationship between body surface area, trough plasma chloramphenicol concentration, and total body chloramphenicol clearance. The hydrolysis of succinate ester to free chloramphenicol may delay the peak free concentration, and its renal elimination (average 21 per cent of the dose administered) significantly affects chloramphenicol pharmacokinetics. The clearance of chloramphenicol exhibited enzyme saturation kinetics in one patient studied at two different doses. Dosage adjustments of intravenous chloramphenicol in children must be made in relation to the trough chloramphenicol plasma concentration, renal elimination of CAP-S, and possible saturation of chloramphenicol metabolism.     

Decreased chloramphenicol clearance in malnourished Ethiopian children

Summary The disposition of chloramphenicol and chloramphenicol monosuccinate has been studied in thirty-four Ethiopian children of varying nutritional status.After a single intravenous dose corresponding to chloramphenicol 25 mg per kg bodyweight, the plasma clearance of chloramphenicol monosuccinate was decreased only in severely malnourished children with kwashiorkor. Seventeen % of the dose (range 0–51%) was recovered in urine as intact prodrug, indicating incomplete and variable bioavailability of chloramphenicol.Compared to underweight children, on average marasmic and kwashiorkor subjects exhibited a 2- and 3-fold increase, respectively, in the AUC of chloramphenicol. Elevated AUCs could be traced to reduced hepatic clearance of the drug. The unbound fraction both of chloramphenicol and its prodrug were slightly elevated in serum from kwashiorkor subjects.The possibility of using a single point measurement of plasma chloramphenicol as a guide to individualized dosage are discussed.     

Clinical pharmacokinetics of chloramphenicol and chloramphenicol succinate

In recent years there has been a renewal of interest in chloramphenicol, predominantly because of the emergence of ampicillin-resistant Haemophilus influenzae, the leading cause of bacterial meningitis in infants and children. Three preparations of chloramphenicol are most commonly used in clinical practice: a crystalline powder for oral administration, a palmitate ester for oral administration as a suspension, and a succinate ester for parenteral administration. Both esters are inactive, requiring hydrolysis to chloramphenicol for anti-bacterial activity. The palmitate ester is hydrolysed in the small intestine to active chloramphenicol prior to absorption. Chloramphenicol succinate acts as a prodrug, being converted to active chloramphenicol while it is circulating in the body. Various assays have been developed to determine the concentration of chloramphenicol in biological fluids. Of these, high-performance liquid chromatographic and radioenzymatic assays are accurate, precise, specific, and have excellent sensitivities for chloramphenicol. They are rapid and have made therapeutic drug monitoring practical for chloramphenicol. The bioavailability of oral crystalline chloramphenicol and chloramphenicol palmitate is approximately 80%. The time for peak plasma concentrations is dependent on particle size and correlates with in vitro dissolution and deaggregation rates. The bioavailability of chloramphenicol after intravenous administration of the succinate ester averages approximately 70%, but the range is quite variable. Incomplete bioavailability is the result of renal excretion of unchanged chloramphenicol succinate prior to it being hydrolysed to active chloramphenicol. Plasma protein binding of chloramphenicol is approximately 60% in healthy adults. The drug is extensively distributed to many tissues and body fluids, including cerebrospinal fluid and breast milk, and it crosses the placenta. Reported mean values for the apparent volume of distribution range from 0.6 to 1.0 L/kg. Most of a chloramphenicol dose is metabolised by the liver to inactive products, the chief metabolite being a glucuronide conjugate; only 5 to 15% of chloramphenicol is excreted unchanged in the urine. The elimination half-life is approximately 4 hours. Inaccurate determinations of the pharmacokinetic parameters may result by incorrectly assuming rapid and complete hydrolysis of chloramphenicol succinate. The pharmacokinetics of chloramphenicol succinate have been described by a 2-compartment model. The reported values for the apparent volume of distribution range from 0.2 to 3.1 L/kg.(ABSTRACT TRUNCATED AT 400 WORDS)     

Genetics and biochemical studies of chloramphenicol-nonproducing mutants of Streptomyces venezuelae carrying plasmid.

Chloramphenicol-nonproducing and plasmid-less mutants obtained previously by treatment with acriflavine still produced a small amount of chloramphenicol in a medium. To study the role of plasmid in chloramphenicol production, 70 chloramphenicol-nonproducing mutants were isolated by acriflavine treatment, high-temperature incubation, UV-irradiation or nitrosoguanidine treatment, starting from a producer (SVM2). Most of them did not produce any amount of chloramphenicol. One mutant, SVM2-2A7 was found to produce 1-deoxychloramphenicol instead of chloramphenicol. The mutations (cpp) affecting chloramphenicol production were analyzed by crosses with a producing strain carrying the complementing auxotrophic markers. Except for the plasmid-less strains, all Cpp mutations including the 1-deoxychloramphenicol-producing mutation were mapped between met and ilv on the chromosome. Additional crosses indicated that these chromosomal cpp mutants still carried the plasmids which had a role in increasing chloramphenicol production. Therefore, it can be concluded that the structural genes for all or most steps of chloramphenicol biosynthesis including the 3-hydroxylation of p-aminophenylalanine are located between met and ilv on the chromosome of S. venezuelae and that the plasmid plays an important role in increasing the chloramphenicol production. The activity of arylamine synthetase involved in the initial step of the chloramphenicol biosynthesis was unrelated to the presence or absence of plasmid. Moreover, the presence of plasmids was not required for host resistance to chloramphenicol.     

茜素共振瑞利散射法测氯霉素的含量

目的建立测定痕量氯霉素的共振瑞利散射法。方法以茜素作探针的共振瑞利散射法测定氯霉素。结果在pH 7.12的Tris-HCl缓冲溶液中,氯霉素和茜素相互作用后,共振瑞利散射显著增强,在373nm处的△IRRS最强。氯霉素的质量浓度在0.097~0.32mg/L范围内与△IRRS成正比,检出限(3Sb/S)为0.080mg/L。结论该法用于氯霉素注射液、滴眼液中氯霉素的测定,结果满意。实现了以廉价试剂、简便方法快速测定痕量药品的目的 。     

依替米星中耳用药后耳蜗功能及形态学初步观察

采用依替米星 (ETM)、氯霉素 (剂量均为 5 0 mg/ kg)和丙二醇溶媒 (0 .2 ml)为对照作中耳腔给药观察耳蜗功能和形态变化 ,结果表明 ETM和氯霉素对听觉功能的影响在统计学上无显著性差异 ,从耳蜗动作电位阈移曲线看 ,氯霉素对听觉功能的影响要比 ETM大一些。 ETM和氯霉素均可引起前庭器官耳石膜耳石变形 ,氯霉素还可造成耳蜗和前庭毛细胞缺失。综合分析 ETM用作滴耳剂优于氯霉素。     

玻璃酸钠在氯霉素滴眼液中的作用

目的研究玻璃酸钠(SH)在氯霉素滴眼液中所起的作用。方法采用对比实验法,测定氯霉素滴眼液和含SH的氯霉素滴眼液的运动黏度。给家兔的2只眼结膜囊内分别滴入氯霉素滴眼液和含SH的氯霉素滴眼液各50μL,采集泪液测定药物浓度,对2种滴眼液做家兔眼刺激实验。结果含SH的氯霉素滴眼液比氯霉素滴眼液的运动黏度大,对眼部不引起刺激性,可以延长药物在泪液中的滞留时间。结论SH能增加氯霉素滴眼液的黏度,延长药物在泪液中的滞留时间,提高药物疗效。     

紫外分光光度法测定复方氯霉素滴耳液中氯霉素含量

目的建立复方氯霉素滴耳液中的氯霉素含量的检测方法。方法采用紫外分光光度法,在278nm波长处直接测定复方氯霉素滴耳液中氯霉素的含量。结果氯霉素在9.6～30μg/mL浓度范围内,吸收度与浓度线性关系良好,r=0.9996;平均回收率为103.47%,RSD为1.57%（n=5）;供试品含量测定RSD为2.5%（n=4）。结论该方法简单、快捷,可用于医院制剂的快速检验。