Elimination of Trimethoprim,Sulphadoxine and their Metabolites in Goats

Abstract The elimination of trimethoprim and sulphadoxine after intravenous administration has been investigated in experiments on goats. Trimethoprim is metabolized to a great extent in the goat liver and the biliary excretion was almost equal to the urinary excretion in experiments with continuous intravenous infusion of trimethoprim. More than 99 % of the amount excreted in bile consists of metabolites of trimethoprim. In contrast it was almost exclusively the unchanged drug which was excreted in the saliva. Sulphadoxine is metabolized to a much smaller extent in goats than trimethoprim and the biliary and salivary excretion seemed without significance in comparison to the urinary excretion.     

Half-life and Renal Excretion of Trimethoprim in Swine

Abstract: Experiments in swine showed that the half-life of trimethoprim was on an average 2 hours 15 minutes and the apparent volume of distribution was 1.4. In addition to glomerular filtration both active tubular secretion and back diffusion are involved in the renal handling of trimethoprim. The back diffusion is greatly influenced by the pH of the urine.     

HPLC法测定头孢羟氨苄甲氧苄啶胶囊中头孢羟氨苄和甲氧苄啶含量的方法改进

目的对高效液相色谱法测定头孢羟氨苄甲氧苄啶胶囊中头孢羟氨苄和甲氧苄啶含量的方法进行改进。方法采用Hypersil ODS2(4.6mm×250mm,5μm)色谱柱,以0.025mol.L-1磷酸(用20%NaOH溶液调节pH值至3.0)-乙腈(88∶12)的流动相,流速:1.0mL.min-1,检测波长为235nm。结果头孢羟氨苄在5.02~351.52μg.mL-1范围内呈良好线性关系,相关系数r=1.0000,平均回收率=100.17%,RSD=0.55%;甲氧苄啶在1.08~75.81μg.mL-1范围内呈良好线性关系,r=0.99994,平均回收率=99.23%,RSD=0.71%。结论本方法简便,结果准确,可靠,可作为该制剂的含量测定方法。     

高效液相色谱法测定增效黄连素胶囊中盐酸小檗碱和甲氧苄氨嘧啶的含量

目的　建立了一种快速、准确的高效液相色谱法同时测定增效黄连素胶囊中盐酸小檗碱和甲氧苄氨嘧啶的含量的方法。 方法 　采用十八烷基健合硅胶为固定相 ;甲醇∶ 1mol· L- 1 醋酸铵溶液 ( 60∶ 40 )为流动相 ;流速 :0 .5 ml· min- 1 ;检测波长 2 90 nm。 结果 　盐酸小檗碱进样量在 0 .160 3 -0 .80 16μg范围内与峰面积呈良好的线性关系 ( r=0 .9999) ,平均回收率为 10 0 .0 5 % ,RSD=0 .2 % ( n=9) ;甲氧苄氨嘧啶在 0 .0 816-0 .40 80μg范围内与峰面积呈良好的线性关系 ( r=0 .9999) ,平均回收率为 99.67% ,RSD=0 .3 % ( n=9)。结论 　实验结果表明本法操作简便 ,重现性好 ,结果准确可靠 ,可以作为样品测定的方法     

高效液相色谱法测定小檗碱甲氧苄啶胶囊中甲氧苄啶含量

目的建立小檗碱甲氧苄啶胶囊中甲氧苄啶的含量测定方法。方法色谱柱为Agelent C18柱(250 mm×4.6 mm,5μm),以甲醇-水(60∶40)为流动相,流速为1.0 mL/min,检测波长为265 nm。结果甲氧苄啶进样量在0.5～1.5μg范围内与峰面积呈良好线性关系,r=0.999 8,平均回收率为98.41%,RSD=1.13%(n=9)。结论该法适用于小檗碱甲氧苄啶胶囊中甲氧苄啶的含量测定。     

甲氧苄啶与3种氨基糖苷类抗生素联用的抗生素后效应

目的:探讨甲氧苄啶 (TMP)与 3种氨基糖苷类抗生素 (庆大霉素、阿米卡星、妥布霉素 )的联合抗生素后效应 (PAE).方法:临床分离大肠埃希氏菌、肺炎克雷伯氏菌各 5株,将 8倍 MIC TMP分别与不同浓度 (1, 2, 4倍 MIC)的 3种抗生素联用,细菌与药物接触 1 h后以微量接种菌落计数法测定 PAE.结果: TMP可使 3种氨基糖苷类抗生素对 2种受试菌的 PAE显著延长,呈相加作用;联合 PAE均呈剂量依赖性.结论: TMP与氨基糖苷类抗生素联合应用可产生明显的 PAE,临床联用具有合理性.     

HPLC法测定克痤隐酮乳膏中甲氧苄啶的含量

目的:建立克痤隐酮乳膏中甲氧苄啶的含量测定方法。方法:高效液相色谱法,迪马C18(200mm×4．6mm,5μm)色谱柱,乙腈-水-三乙胺(200:799:1)(用氢氧化钠试液或冰醋酸调节溶液pH值至5．9)为流动相,检测波长为288nm。结果:甲氧苄啶在0．7584μg-1．7696μg范围内进样量与峰面积线性关系良好,平均回收率为99．1％, RSD为1．43％,准确度高。结论:本方法简便、准确,可测定克痤隐酮乳膏中甲氧苄啶的含量。     

高效液相色谱法测定复方庆大霉素注射液中甲氧苄啶含量

目的：建立高效液相色谱法(HPLC法)，直接测定复方庆大霉素注射液中的甲氧苄啶含量。方法：采用C18柱，以pH=3．5的醋酸钠缓冲液—甲醇(77：23)为流动相，检测波长为271nm。结果：甲氧苄啶进样量在0．64～0．96μg范围内与主峰面积线性关系良好(r=0．9997)，平均回收率为99．9％，重复进样RSD为0．5％(n=6)。结论：该方法专属性强，简便快速，结果准确。     

HPLC法测定甲氧苄啶片主药及有关物质的含量

目的:建立高效液相色谱法测定甲氧苄啶片中主药及有关物质的含量。方法:色谱柱为Waters symmetry C18,流动相为峰0.0能15有m效ol·分L离-1磷;甲酸(氧p苄H啶3.5检)-测乙浓腈度(8线3:性17范),围检为测波16长.1～为126711.3nμmg,·流m速L-为(1r1=.00m.9L9·9m9i,nn-=1,柱5)温;平为均30回℃收。率结为果1:0甲0.4氧%苄,R啶S与D=其0相.7%邻(杂n=质9);有关物质含量<0.6%。结论:该方法简便、准确,专属性强,可用于甲氧苄啶片的含量测定及有关物质的检查。     

Elimination of Trimethoprim in Swine: Comparison of Results Obtained by Three Analytical Methods

Abstract: ¹⁴C-trimethoprim was administered to swine by intravenous injection. The concentration of trimethoprim in the plasma was determined by spectrophotometry, spectrofluorimetry and by liquid scintillation counting. There were only minor deviations between the spectrophotometric and the spectrofluori-metric methods, as the metabolites which may interfere in the spectrophotometric analysis are formed only in very small amounts. More than 50 % of the administered dose was excreted in the urine within 5 hours. The total urinary excretion in 3 days was 75–80 % while only about 10 % was excreted in the faeces. Trimethoprim was extensively metabolized in swine. Less than 15 % of the dose was excreted unchanged in the urine.     

头孢羟氨苄甲氧苄啶分散片的含量测定研究

在试制头头抱弪氨苄甲氧苄啶分散片中,为确保其药品质量要制定测定其含量的方法,我们通过对其含量测定中的波长选择线性关系试验、回收率试验、溶液稳定性试验、精密度试验、重复性试验等方法学研究确定了用高效液相法测定其头孢氨苄及甲氧苄啶含量的方法．并经对样品及中试放大产品的研究确认该方法可靠适用。     

头孢羟氨苄甲氧苄啶分散片的含量测定研究

在试制头孢羟氨苄甲氧苄啶分散片中,为确保其药品质量要制定测定其含量的方法,我们通过对其含量测定中的波长选择线性关系试验、回收率试验、溶液稳定性试验、精密度试验、重复性试验等方法学研究确定了用高效液相法测定其头孢氨苄及甲氧苄啶含量的方法．并经对样品及中试放大产品的研究确认该方法可靠适用。     

甲氧苄啶注射液无菌检查方法学研究

目的建立甲氧苄啶注射液无菌检查方法。方法按《中国药典》2005年版无菌检查法验证实验的有关要求,取供试品10支.膜-1（批出厂检验量）按薄膜过滤法过滤,再用0.1%无菌蛋白胨水溶液分次冲洗,每膜不少于400mL,阳性对照菌为大肠埃希菌。结果经方法验证,供试品阴性组、阴性对照组均无菌生长,供试品7种阳性菌试验组各滤器中试验菌与阳性菌对照组比较均生长良好,说明供试品的检验量在该检验条件下已消除其抑菌作用或其抑菌作用可以忽略不计。结论本法简便、科学可靠,可作为甲氧苄啶注射液的常规无菌检查方法。     

自身对照法测定头孢氨苄甲氧苄啶胶囊溶出度

目的建立头孢氨苄甲氧苄啶胶囊溶出度测定方法。方法分别采用自身对照法与对照品对照法测定头孢氨苄甲氧苄啶胶囊的溶出度。结果头孢氨苄甲氧苄啶胶囊溶出度测定自身对照法在8.6～86μg.mL-1呈线性(r=0.9999,n=6),回收率101.9%,RSD=0.5%;与对照品对照法相比简便易行,同时也能反映样品溶出的真实情况,达到质量控制目的。结论本法稳定、简便、准确、可行。     

HPLC法测定联磺甲氧苄啶片的含量

目的建立了同时测定联磺甲氧苄啶片中3个组分含量的高效液相色谱法。方法色谱柱为DikmaDiamonsil C18;流动相为甲醇-乙酸铵溶液（33∶67）,检测波长为210nm;流速为1mL.min-1。结果磺胺甲噁唑、磺胺嘧啶和甲氧苄啶的线性范围分别为50~150μg.mL-1（r=1.000）、50~150μg.mL-1（r=0.9999）、10~30μg.mL-1（r=0.9998）;平均回收率分别为101.6%（RSD=1.20%,n=9）、98.4%（RSD=0.95%,n=9）、98.7%（RSD=1.03%,n=9）。结论本法简单、快速、准确,可用于联磺甲氧苄啶片的定量分析。     

Trimethoprim,Metioprim, Tetroxoprim,and RO 10-5970 in Canine Bone

Abstract: The penetration of trimethoprim and three derivatives into bone tissue was investigated in a dog model. Our data demonstrated that the trimethoprim derivative RO 10–5970 concentrates well in bone tissue with median tissue-to-serum concentration ratios of 0.23 in cortical bone and 0.81 in both medulla and cancellous bone. The use of RO 10–5970 in osseous infections is appealing because oral administration is possible; therefore, clinical trials appear warranted.     

短毛细管区带电泳快速测定增效联磺片中三组分含量

目的:在短毛细管上应用毛细管区带电泳法快速测定增效联磺片中磺胺甲嗯唑(SMZ)、磺胺嘧啶(SD)及甲氧苄氨嘧啶(TMP)三组分的含量。方法:采用未涂层弹性石英毛细管(35cm×50 μm,有效长度20 cm),以咖啡因为内标(IS),检测波长214 nm(0.01 AUFS),电压10 kV,重力进样(10 cm×5 s),温度15℃,运行缓冲液为20 mmol·L-1硼砂溶液(磷酸调pH6.0)。每次电泳运行前用0.1 mol·L-1氢氧化钠溶液、水及缓冲溶液各冲洗毛细管3 min。结果:SMZ、SD、TMP的线性范围分别为0.0398-0.199,0.0399-0.200,0.0160-0.0800 mg·mL-1。平均回收率(n=9)分别为99.4％,99.0％,99.8％;RSD均小于1.5％。结论:该法简便快捷,准确可靠,灵敏度高。     

Influence of Crystal Habit on Trimethoprim Suspension Formulation

Purpose. The role of crystal habit in influencing the physical stability and pharmacokinetics of trimethoprim suspensions was examined. Methods. Different habits of trimethoprim (TMP) were obtained by recrystallizing the commercial sample (PD) utilizing solvent-change precipitation method. Four distinct habits (microscopic observation) belonging to the same polymorphic state (DSC studies) were selected for studies. Preformulation and formulation studies were carried out on suspension dosage forms containing these crystals. The freshly prepared suspensions were also evaluated for their pharmacokinetic behaviour on healthy human volunteers using a cross over study. Results. Variation of crystallization conditions produces different habits of TMP. Among the different crystal habits exhibiting same polymorphic state, the most anisometric crystal showed best physical stability in terms of sedimentation volume and redispersibility. However, habit did not significantly affect the extent of TMP excreted in urine. Conclusions. Modification of surface morphology without significantly altering the polymorphic state can be utilized for improving physical stability of TMP suspensions. However, the pharmacokinetic profile remains unaltered.     

Development and Validation of a Stability-Indicating HPLC Method for the Simultaneous Determination of Sulfadiazine Sodium and Trimethoprim in Injectable Solution Formulation

A direct, precise, and stability-indicating HPLC method that is based on reversed-phase liquid chromatography (RP-HPLC) coupled with a photodiode array detector (PDA) was developed, optimized, and validated for the simultaneous determination of sulfadiazine sodium (SDZS) and Trimethoprim (TMP) in Bactizine® forte injectable solution. The separation was achieved using a C18 column (250 mm×4.6 mm i.d., 5 μm particle size) at room temperature, and an isocratic mobile phase that consisted of a trinary solvent mixture of water–acetonitrile–triethylamine (838:160:2, v/v) at pH 5.5 ± 0.05. The mobile phase was delivered at 1.4 ml/min and the analytes were monitored at 254 nm. The effects of the operational chromatographic conditions on the peak’s USP tailing factor, column efficiency, and resolution were systematically optimized. Forced degradation experiments were carried out by exposing SDZS, TMP standards, and their formulation to thermal, photolytic, oxidative, and acid-base hydrolytic stress conditions. The method was successfully validated in accordance to International Conference on Harmonization (ICH) and United States Pharmacopoeia (USP34/NF29) guidelines and found to be suitable for the quantitative determination and stability of SDZS and TMP in Bactizine® forte injectable solution.     

HPLC法同时测定磺啶新林胶囊中4个成分的含量

目的:建立同时测定磺啶新林胶囊中盐酸溴己新、盐酸氯丙那林、磺胺甲噁唑和甲氧苄啶含量的方法。方法:采用高效液相色谱法,Ecosil-C₁₈色谱柱（4.6 mm×250 mm,5μm）,以乙腈-0.001 5 mol·L^-1十二烷基硫酸钠的0.1%三乙胺溶液（用磷酸调pH值至3.0）（52:48）为流动相,流量1.0 mL·min^-1,检测波长为215 nm。结果:4个成分的峰面积与浓度的线性关系良好（r>0.999 9）;加样回收率为98.85%⁹9.58%。结论:该方法可用于磺啶新林胶囊中盐酸溴已新、盐酸氯丙那林、磺胺甲噁唑和甲氧苄啶4个成分的含量测定。