Determination of interstitial rocuronium concentrations in the muscle tissue of anesthetized dogs by microdialysis

INTRODUCTION: The objective was to establish and validate a microdialysis technique for the quantification of interstitial concentrations of the neuromuscular blocker, rocuronium, in the muscle tissue of dogs under steady-state conditions. METHODS: The standard and combined retrodialysis approaches were used for in vivo microdialysis probe calibration. After induction of anesthesia with pentobarbital (30 mg/kg), the left femoral vein was cannulated and blood drawn for protein binding determination. Microdialysis probes were inserted in the muscle and calibrated in vivo, using vecuronium as the calibrator. Each dog received a short 2-min infusion followed by a 120-min infusion of rocuronium via the right jugular vein and three microdialysis samples were collected at steady-state during a 2-h period. Samples were stored at -70 degrees C until HPLC analysis. RESULTS: Using combined retrodialysis, rocuronium unbound interstitial (C(ISFu)) and venous plasma (C(pssuv)) concentrations are in good agreement; with a ratio C(ISFu)/C(pssuv) of 100+/-11%. Using standard retrodialysis, this ratio was 47+/-7%. CONCLUSIONS: Combined retrodialysis is a more reliable and accurate technique for quantitative assessment of rocuronium interstitial concentrations especially for lengthy anesthetic procedures. These findings have potential implications, as drug concentrations in the site of action would be more relevant for concentration-effect relation of muscle relaxants.     

Evaluation of gatifloxacin penetration into skeletal muscle and lung by microdialysis in rats

This study aimed to investigate gatifloxacin distribution into skeletal muscle and lung interstitial fluid by microdialysis and to correlate free tissue and free plasma levels of the drug. Microdialysis recoveries were determined in vitro by extraction efficiency and retrodialysis at 80, 160 and 400 ng/ml resulting in 33.5+/-1.3%, 33.1+/-1.2%, 31.8+/-2.7% and 31.4+/-2.6%, 33.1+/-2.2%, 30.6+/-3.3%, respectively. In vivo recovery by retrodialysis in Wistar rats' skeletal muscle and lung were 29.1+/-1.0% and 30.7+/-1.4%, respectively. The recovery was constant and independent on the method or media used. Gatifloxacin tissue penetration was investigated after intravenous dosing of 6 mg/kg to Wistar rats. Free skeletal muscle, lung and plasma profiles were virtually superimposable resulting in similar area under the curve (AUC(0-9)) of 3888+/-734 ng h/ml, 4138+/-1071 ng h/ml and 3805+/-577 ng h/ml, respectively (alpha=0.05). The tissue distribution factors were 1.02 and 1.08 for muscle and lung relative to plasma. In conclusion, free plasma levels are a good surrogate for gatifloxacin active levels at the infection site.     

Pharmacologic modulation of skeletal muscle metabolism: a microdialysis study

Microdialysis is a valuable tool to measure tissue responses. We hypothesized that skeletal muscle metabolism can be modulated by microdialysis applied drugs which alter cytosolic calcium concentration. With approval of the local animal care committee, the hind limbs of sacrificed male Sprague Dawley rats were perfused either with Ringer's solution or with dantrolene 1 microM at 30 ml hr(-1) and 21 degrees. Microdialysis probes in both hind limbs were perfused at 1 microl min(-1) either with sorbitol 80 mM, calcium 20 mM, 40 mM, 80 mM, caffeine 40 mM, 80 mM, and halothane 10 vol% respectively, and at the contralateral adductor muscle with Ringer as control. Lactate was measured spectrophotometrically in the dialysate at 15 min. intervals. Lactate levels as measured by intramuscular microdialysis were not influenced by intramuscular application of sorbitol 80 mM compared to control measurements with Ringer's solution. Local application of calcium 20 mM, 40 mM, 80 mM, caffeine 40 mM, 80 mM, and halothane 10 vol% via microdialysis increased lactate concentrations, while organ perfusion by dantrolene 1 microM reduced the caffeine-induced lactate increase. Modulation of intramuscular lactate metabolism by exogenous compounds via microdialysis probes generates new insights in skeletal muscle metabolism.     

HPLC法测定谷氨酸诺氟沙星注射液的有关物质及含量

目的 采用HPLC法测定谷氨酸诺氟沙星注射液的有关物质及含量.方法 采用ODS柱,以0.025 mol·L-1磷酸溶液(用三乙胺调节Ph值至3.0)-乙腈(84∶16)为流动相,检测波长为278 nm.谷氨酸诺氟沙星在18.8～93.9 mg·L-1范围内线性关系良好(r=0.999 8),检测限为0.298 ng,平均回收率为99.80%,RSD为0.59%.结果 在本文所设计的实验条件下,有关物质检查的专属性较好.在含量测定条件下,该方法的线性范围、回收率、精密度、重复性、耐用性及稳定性的考察结果都较满意.结论 采用HPLC法对谷氨酸诺氟沙星注射液的有关物质和含量进行测定具有专属性强,结果准确及操作简便等优点.     

差示扫描电位法测定诺氟沙星的含量

本文介绍了差示扫描电位法在药物分析中的应用,并测定了诺氟沙星的含量,同时与紫外分光光度法进行了比较。结果表明:差示扫描电位法所需的设备简单,灵敏度高,结果可靠,可作为弱酸弱碱药物含量测定的一种新方法。     

高效液相色谱法测定复方白氟膜剂中诺氟沙星的含量

目的建立复方白氟膜剂中诺氟沙星含量的HPLC测定方法.方法色谱柱为Xterra RP18柱(3.9mm×150mm,5μm);流动相为乙腈-0.025mol/L磷酸溶液(13:87);检测波长为278nm;柱温为40℃;流速1.0mL/min.结果氟哌酸在0.172～3.432μg内,峰面积与进样量呈良好的线性关系(r=0.999 98,n=3),平均加样回收率为102.20%(RSD=1.52%,n=6).结论本方法简便、准确、重现性好,可作为该制剂的质量控制标准.     

Determination of norfloxacin by highly accurate nephelometric titration

A highly accurate nephelometric titration for the determination of norfloxacin is presented. The titration operating conditions were studied and the solubility product constant of norfloxacin-tetraphenylboron precipitation was determined. The result of the titration is comparable to those of control experiments. The proposed method has been found to be accurate, precise, specific, and linear.     

Dose ranging pharmacokinetics and brain distribution of norfloxacin using microdialysis in rats

The purpose of this study was to investigate the effect of dose on norfloxacin pharmacokinetics and distribution into the brain extracellular fluid (ECF), in freely moving rats. Unbound concentrations of norfloxacin in hippocampus were determined by microdialysis after an i.v. bolus dose of 12.5, 25, 50, 100, or 150 mg/kg in rats. In vivo recovery of norfloxacin was determined by retrodialysis by calibrator. Among three fluoroquinolones (enoxacin, pefloxacin, and ciprofloxacin) selected as potential calibrators, ciprofloxacin was selected as the best one. Maximum ECF brain norfloxacin concentrations are rapidly obtained but the ECFbrain/plasma areas under curves (AUC) ratios are low and independent of dose with a mean value of 8.2 +/- 5.8%. By contrast, norfloxacin systemic pharmacokinetics was nonlinear, with total plasma clearance decreasing significantly from 23.0 +/- 3.4 to 14.4 +/- 3.8 mL/min/kg when dose increased from 12.5 to 150 mg/kg.     

紫外分光光度法测定诺氟沙星眼药水含量

本文研究了用紫外分光光度法测定诺氟沙星眼药水中诺氟沙星的含量,选用pH5.8磷酸盐缓冲液为溶剂,测定波长315nm。吸收系数(E_(1cm)~(1%))为393,测得平均回收率为99.8%,CV=0.43%(n=5)。眼药水附加剂对测定无干扰。     

荧光分光光度法测定血清中诺氟沙星浓度

本文采用荧光分光光度法测定血清中诺氟沙星浓度。用三氯醋酸为蛋白沉淀剂，以ＮａＯＨ调ｐＨ至弱酸性，加醋酸－醋酸钠缓冲液后测荧光强度。激发波长为３３５ｎｍ，发射波长为４５０ｎｍ，浓度在０～８μｇ／ｍｌ范围内呈良好线性关系，标准曲线的回归方程为Ｙ＝０．００２３＋０．０２３４ｘ，相关系数ｒ＝０．９９９２，平均回收率为９６．３％，变异系数为４．１６％。     

地塞米松对大鼠骨骼肌间质中成纤维细胞增殖的影响

目的：探讨糖皮质激素局部注射治疗婴幼儿先天性斜颈的机理。方法：体外培养Wistar大鼠乳鼠骨骼肌间质成纤维细胞，采用3H－TdR掺入法，MTT比色法和流式细胞仪细胞周期分析技术，观察地塞米松对成纤维细胞DNA合成、细胞数目和细胞周期的影响。结果：在体外培养条件下，地塞米松可抑制成纤维细胞DNA合成，减少成纤维细胞增殖数目，降低成纤维细胞增殖指数，其作用随浓度增大而增强，结论：先天性斜颈婴幼儿期胸锁乳突肌局部注射糖皮质激素，可抑制胸锁乳突肌间质成纤维细胞的过度增生，减少肌肉纤维化。     

高效液相色谱法测定甲诺参洗剂中甲硝唑及诺氟沙星的含量

目的:建立同时测定甲诺参洗剂中甲硝唑和诺氟沙星含量的高效液相色谱法.方法:采用Kromasil C 18 色谱柱(250 mm× 4.6 mm,5 μm),0.7%三乙胺(以磷酸调pH至 3.0 )-甲醇(200∶300)为流动相,流速为 1.0 mL·min -1 ,检测波长为290 nm.结果:甲硝唑在 20.0 ～ 150.0 mg·L -1 范围内,峰面积与其浓度线性关系良好(r= 0.999 9 ),平均回收率为 100.4% ,重复性试验RSD为 0.4% (n=5),检测限为 4.0 ×10 -3 μg;诺氟沙星在 10.0 ～ 75.0 mg·L -1 的范围内,峰面积与其浓度线性关系良好(r= 0.999 9 ),平均回收率为 98.6% ,重复性试验RSD为 0.5% (n=5),检测限为 2.0 ×10 -3 μg.结论:本法准确、简便、快速,具有专属性强,灵敏度高的特点,适用于含甲硝唑及诺氟沙星制剂的含量测定.     

反相高效液相色谱法测定诺氟沙星锌干混悬剂的含量

目的建立一种测定诺氟沙星锌(NF-Zn)干混悬剂含量的RP-HPLC.方法采用Lichrospher5-C18柱(200mm×4.6mm),0.025mol/L磷酸溶液-乙腈(87:13)为流动相,检测波长为278nm,流速为0.8mL/min.结果该法能较好地测定NF-Zn的含量.方法回收率为(99.37±0.42)%,最低检出限为0.2ng,日间、日内RSD均小于1.2%,在11.01～137.60μg/mL浓度范围内线性关系良好,线性方程为y=-1.681 65 8.931 54×10-6X,r=0.999 8.结论该法专属性好,简捷,快速准确,适用于该产品质量分析控制.     

流动注射化学发光法测定药物制剂中的诺氟沙星含量

目的建立药物制剂中诺氟沙星的流动注射化学发光测定法。方法选择氢氧化钠溶液为介质,选择鲁米诺,高碘酸钾为反应剂,采用流动注射化学发光法测定诺氟沙星。结果选择鲁米诺浓度5．0×10-5mol／L,高碘酸钾浓度6．0×10mol／L,可在试剂消耗最少的情况下得到最强发光信号。诺氟沙星浓度与化学发光信号范围线性为5．0×10-8～2．0×10-6mol／L,检出限为1．8×10mg／L,回收率96．0％～101．5％,相对标准偏差1．59％～2．04％。结论该方法简便快捷、灵敏度高,可用于药物制剂中诺氟沙星的含量检测。     

游离骨骼肌自体移植的肌纤维型分布、组织化学及组织形态学实验研究

目的研究实验动物游离骨骼肌自体移植的肌纤维型分布、组织化学及组织形态学变化。方法肌肉移植分为两期 :第一期去除支配移植肌的神经 ,第二期 3周后行肌肉移植。肌肉标本取材于手术时及术后 6周、10周 ,以肌球蛋白ATP酶染色 (pH9 4)将肌纤维分为Ⅰ型和Ⅱ型。组织化学和组织形态学分别用相应方法检测。超微结构用电镜观察。结果桡侧腕屈肌中Ⅰ型肌纤维百分率从移植后 6周时的 11 0 0± 1 80增加到 10周的 19 82± 2 38;股薄肌中Ⅰ型肌纤维百分率从移植后6周时的 10 91± 1 80增加到 10周的 15 48± 2 0 0。肌肉移植后 6周时两块移植肌中Ⅰ型肌纤维分布差异无显著意义 (P >0 0 5 ) ,10周时差异有显著性意义 (P <0 0 1)。组织化学从正常变化转为去神经后 3周时降低或消失 ,肌肉移植后又逐渐恢复。组织形态学为肌肉移植后通过肌细胞再生逐渐恢复。结论同型肌纤维游离骨骼肌自体移植后Ⅰ型肌纤维分布多于不同型肌纤维骨骼肌移植 ,功能恢复亦为同型肌纤维骨骼肌移植优于不同型肌纤维骨骼肌移植。目的研究实验动物游离骨骼肌自体移植的肌纤维型分布、组织化学及组织形态学变化。方法肌肉移植分为两期 :第一期去除支配移植肌的神经 ,第二期 3周后行肌肉移植。肌肉标本取材于手术时及术后 6周、10周 ,以     

游离脂肪酸与骨骼肌胰岛素抵抗的研究进展

胰岛素抵抗与肥胖、2型糖尿病、高血压、脂代谢紊乱、异常血凝及纤溶等代谢综合征的发生和发展密切相关。虽然胰岛素抵抗发生机制尚不完全清楚,但大量研究表明游离脂肪酸在机体胰岛素抵抗,特别是骨骼肌胰岛素抵抗方面发挥重要作用。本文就游离脂肪酸引起骨骼肌胰岛素抵抗的作用及其机制进行综述,以期为胰岛素抵抗的改善及治疗带来新的手段。     

一阶导数紫外分光光度法测定诺氟沙星胶囊的含量

采用一阶导数紫外分光光度法测定胶囊中诺氟沙星的含量,可排除辅料的干扰,测定方法简便,快速,测定结果准确可靠。该法与药典的非水滴定法测定结果相一致,值得进一步推广使用。     

双波长分光光度法测定栓剂中甲硝唑,诺氟沙星的含量

本文采用双波长分光光度法同时测定栓剂中甲硝唑、诺氟沙星的含量；甲硝唑的测定波长为３１３．０ｎｍ，参比波长为２６１．５ｎｍ，诺氟沙星的测定波长为２８３．５ｎｍ，参比波长为３４０．５ｎｍ，甲硝唑的平均回４文率为１００．７４％，ＲＳＤ为０．７１％；诺氟沙星的平均回收率为１００．０５％，ＲＳＤ为０．６５％。该法快速、简便，结果准确，适用于该制剂质量控制。