Stability of cefazolin sodium in polypropylene syringes and polyvinylchloride minibags

Background:

Cefazolin is a semisynthetic penicillin derivative with a narrow spectrum of activity covering some gram-positive organisms and a few gram-negative aerobic bacteria.

Objective:

To determine the physical and chemical stability of cefazolin sodium reconstituted with sterile water for injection and stored in polypropylene syringes or diluted with either 5% dextrose in water (D5W) or 0.9% sodium chloride (normal saline [NS]) and stored in polyvinylchloride (PVC) minibags.

Methods:

Reconstituted solutions of cefazolin (100 or 200 mg/mL) were packaged in polypropylene syringes. More dilute solutions (20 or 40 mg/mL) were prepared in D5W or NS and packaged in PVC minibags. For each concentration–diluent–container combination, 3 containers were designated for each day of analysis (days 7, 14, 21, and 30). Containers were stored under refrigeration (5°C) with protection from light until the designated day of analysis, at which time one 5-mL sample was collected from each the designated container. The designated containers were then stored at room temperature (21°C to 25°C) with exposure to light for an additional 72 h, and additional samples were drawn. The samples were assayed using a validated, stability-indicating high-performance liquid chromatography method. The colour and clarity of the solutions, as well as their pH, were also monitored on each sampling day.

Results:

All samples remained clear for the duration of the study; they had a slight yellow colour that darkened over time, and there was an increase in pH. Solutions diluted with sterile water for injection and stored in polypropylene syringes retained at least 94.5% of the initial concentration after 30 days of refrigerated storage and at least 92.1% after an additional 72 h at room temperature with exposure to light. Samples diluted in D5W or NS and stored in PVC minibags retained at least 95.8% of the initial concentration after 30 days of refrigerated storage and at least 91.8% after an additional 72 h at room temperature with exposure to light.

Conclusions:

Cefazolin at various concentrations stored in polypropylene syringes or PVC minibags was stable for up to 30 days with storage at 5°C with protection from light, followed by an additional 72 h at 21°C to 25°C with exposure to light.     

Stability of pantoprazole sodium in glass vials, polyvinyl chloride minibags, and polypropylene syringes

Background:

Pantoprazole sodium, a proton-pump inhibitor, is approved for the short-term treatment of several types of ulcer, Zollinger–Ellison syndrome, and gastroesophageal reflux disease.

Objective:

To determine the physical compatibility and chemical stability of ethylenediaminetetra-acetic acid (EDTA)–free pantoprazole in glass vials, polypropylene syringes, and polyvinylchloride (PVC) minibags, after storage at 2°C to 8°C with protection from light or at 20°C to 25°C with exposure to light.

Methods:

Solutions of pantoprazole 4 mg/mL reconstituted in 0.9% sodium chloride (normal saline [NS]) were stored in glass vials at 20°C to 25°C. Similar solutions were transferred to polypropylene syringes and stored at 2°C to 8°C. Stock solution was further diluted, in 5% dextrose in water (D5W) or NS, to 0.4 or 0.8 mg/mL, and samples were then packaged in PVC minibags for storage at 2°C to 8°C or at 20°C to 25°C. Samples collected on days 0, 2, 3, 7, 14, 21, and 28 were analyzed in duplicate with a stability-indicating high-performance liquid chromatography assay.

Results:

Pantoprazole 4 mg/mL was stable (i.e., retained at least 90% of initial concentration) for 3 days when stored in glass vials at 20°C to 25°C or for 28 days when stored in polypropylene syringes at 2°C to 8°C. Pantoprazole 0.4 mg/mL diluted in D5W and stored in PVC minibags was stable for 2 days at 20°C to 25°C or for 14 days at 2°C to 8°C. At 0.8 mg/mL, pantoprazole in D5W was stable for 3 days at 20°C to 25°C or 28 days at 2°C to 8°C. Pantoprazole diluted to either 0.4 or 0.8 mg/mL in NS and stored in PVC minibags was stable for 3 days at 20°C to 25°C or 28 days at 2°C to 8°C.

Conclusions:

The present study confirmed or extended previously reported expiry dates for pantoprazole sodium packaged in glass vials, polypropylene syringes, and PVC minibags.     

注射用五水头孢唑林钠与盐酸利多卡因体外配伍稳定性考察

目的:考察在 4℃和 25℃条件下五水头孢唑啉钠在灭菌注射用水、氯化钠、利多卡因中的兼容性和稳定性。方法:五水头孢唑啉钠分别溶于灭菌注射用水、氯化钠、利多卡因,浓度均为临床常用浓度,分别保存在4℃和 25℃条件下,配制后0,2,4,8,24,48 h时检查每个样品内部是否有沉淀、云状物、变色,并测定样品pH值。使用新建立的高效液相色谱法检测配伍液中的药物浓度。结果:经过48 h储存,五水头孢唑啉钠与利多卡因溶液在4℃避光条件下均无浑浊、无沉淀、无云状物、无气泡、不变色,pH 值保持较稳定,主药含量均大于90%;在 25℃条件下,五水头孢唑啉钠与水、氯化钠溶液在 24 h后开始变黄,48 h后颜色加深,水溶液和盐溶液pH值均显著上升。结论:从外观、pH值、主药含量稳定性结果表明,4℃五水头孢唑林钠和盐酸利多卡因的配伍液的稳定性好,为临床上使用五水头孢唑林钠与利多卡因在肌注时进行配伍使用,从而达到缓解肌注疼痛提供可行的体外试验证据。     

利多卡因凝胶贴膏的制备与质量评价

目的:制备利多卡因凝胶贴膏,并对其质量进行考察。方法:采用正交设计法,以初黏力、持黏力、剥离强度和感官评价的综合评分为指标优化处方;采用高效液相色谱法进行含量测定及体外释放度研究。结果:最佳基质处方为甘羟铝∶聚丙烯酸钠∶高岭土∶明胶=0. 3∶5∶7∶2. 5,3批样品的含量测定结果为100. 6%,99. 8%,100. 2%; 6 h平均累积释放率分别为(91. 47%±3. 52%),(92. 41%±4. 25%)和(90. 14%±4. 18%),n=6; 30℃放置6个月黏附性及主药含量无显著改变。结论:该方法制备的利多卡因凝胶贴膏外观平整,质量稳定、可控。     

盐酸山莨菪碱对头孢拉定注射液稳定性的影响

目的:研究盐酸山莨菪碱(654-2)对头孢拉定(Cep)注射液稳定性的影响.方法:采用反相高效液相色谱法测定3种温度F,不同时间的Cep在生理盐水和含654-2盐水中的含量.结果:两组数据经统计学处理无显著性差异.结论:Cep与654-2配伍时其含量稳定.     

盐酸肾上腺素注射液中S-对映体的测定及稳定性考察

目的:建立肾上腺素对映异构体中S-对映体的高效毛细管电泳检测方法。方法:采用未涂层熔融石英毛细管(50μm×42 cm,有效长度32 cm),以含13 mmol·L-1DM-β-CD pH 2.5的缓冲体系(含0.10 mol·L-1磷酸和0.07 mol·L-1三乙胺)为背景电解质溶液,在20 kV分离电压下,于214 nm波长处测定S-对映体。结果:肾上腺素R-对映体和S-对映体浓度分别在0.0026～0.1036 mg·mL-1范围内线性关系良好,相关系数分别为0.9995和0.9999(n=6);定量限分别为0.3和0.4μg·mL-1(S/N≥10),检测限分别为0.1μg·mL-1(S/N≥3)。结论:本方法灵敏度高,重复性好,可用于盐酸肾上腺素注射液中S-对映体的测定及稳定性研究。     

Stability of trisodium citrate and gentamicin solution for catheter locks after storage in plastic syringes at room temperature

Background:

Catheter-related infections are a major problem for hemodialysis patients with central venous catheters for vascular access. Catheter lock solutions containing an anticoagulant are used to maintain the patency of the catheter between hemodialysis sessions. There is evidence that the use of lock solutions containing an antibiotic is associated with lower rates of infection but also that these solutions can kill microbes in colonized catheters and thus avoid the risks and costs associated with replacing the catheter.

Objective:

This stability study was conducted to determine whether an extemporaneously prepared gentamicin–citrate catheter lock solution would retain its potency over time, thus allowing for advance preparation of the solution.

Methods:

Catheter lock solutions containing gentamicin alone, citrate alone, and the combination of gentamicin and citrate were prepared aseptically and packaged in polyethylene syringes. The syringes were stored at room temperature. At timed intervals over 112 days, samples were withdrawn for analysis by means of validated high-performance liquid chromatography.

Results:

None of the 3 lock solutions showed any evidence of degradation during the 112-day observation period. In the formulation containing both gentamicin 2.5 mg/mL and sodium citrate 40 mg/mL (4%), there was no change in the concentration of either gentamicin (p = 0.34) or citrate (p = 0.55). Linear regression analysis of the concentration–time data for the combined formulation showed that 99.97% of the labelled amount of gentamicin and 101.30% of the labelled amount of citrate remained at day 112. The lower limit of the 95% confidence intervals indicated that more than 98.17% of the gentamicin and more than 99.57% of the citrate remained on day 112.

Conclusion:

The results of this study will allow pharmacies to extemporaneously compound the combined gentamicin–citrate catheter lock solution in advance of use. The method described here will yield a stable product for use in clinical applications.     

复方盐酸利多卡因温敏凝胶的制备和含量测定

目的：制备复方盐酸利多卡因温敏凝胶,并建立其含量测定方法。方法：将盐酸利多卡因和盐酸罗哌卡因组成复方,制成温敏凝胶,用HPLC法同时测定其中盐酸利多卡因和盐酸罗哌卡因的含量。色谱柱：Athena C18-WP柱（200 mm×4.6 mm,5 μm）;流动相：乙腈-0.02 mol/L磷酸二氢钠-三乙胺（48∶52∶0.15,用磷酸调节pH值至3.15）;检测波长：220 nm;流速：1.0 ml/min。结果：复方盐酸利多卡因温敏凝胶为无色澄明液体,相变温度为32 ℃。盐酸利多卡因的线性回归方程为A=3.97×104c＋2.44×104（r=0.999 9）,线性范围5.04~80.64 μg/ml;盐酸罗哌卡因的线性回归方程为A=3.93×104c＋1.21×103（r=0.999 9）,线性范围2.03~32.48 μg/ml。HPLC法的精密度和准确度良好。凝胶中盐酸利多卡因和盐酸罗哌卡因的含量分别为标示量的 （97.89±1.32）%和（99.61±1.97）%（n=3）。结论：复方盐酸利多卡因温敏凝胶质量可控,是一种值得开发的新制剂。     

用RP-HPLC法测定三利乳膏中盐酸利多卡因的含量

目的:建立测定三利乳膏中盐酸利多卡因含量的RP-HPLC法。方法:色谱柱为Kromasil-C18(150 mm×4.6 mm,5μm);流动相为乙腈-0.02 mol/L磷酸二氢钠-三乙胺(47∶53∶0.15),用磷酸调节pH值至3.15,内含0.015 mol/L十二烷基硫酸钠(SDS);检测波长220 nm;流速1.0 ml/min。结果:盐酸利多卡因在6.576~87.68μg/ml的线性关系良好(r=0.999 7,n=3),低、中、高三种浓度的回收率分别为(99.78±1.14)%、(98.91±1.78)%、(100.77±2.32)%。结论:该方法简便、准确,重复性好,适用于三利乳膏的质量控制。     

盐酸甲氯芬酯与3种含果糖输液配伍的稳定性考察

目的考察盐酸甲氯芬酯在果糖,果糖氯化钠,转化糖输液中配伍的稳定性。方法分别配制输液置恒温水浴箱中,以高效液相色谱法测定甲氯芬酯含量,以酸度计测量混合输液的pH值。结果在25℃下,6h内3种输液的外观无变化,pH值稍有变化;甲氯芬酯的含量在果糖中6h稳定,转化糖中2h稳定,果糖氯化钠中1h稳定。结论实验输液的pH值及含量变化提示,盐酸甲氯芬酯与果糖、转化糖注射液配伍后宜2h内使用,与果糖氯化钠配伍后宜1h内使用。     

肌苷口服液杂质分析及肌苷溶液的稳定性研究

目的分析影响肌苷口服液澄明度的主要原因,并考察2%肌苷溶液在加热情况下和碱性条件下的稳定性。方法用高效液相色谱法确认肌苷口服液中的杂质,并通过测定2%肌苷溶液在不同时间不同条件下的含量来考察其稳定性。结果肌苷口服液中主要杂质为次黄嘌呤,2%肌苷溶液在60℃以下和弱碱性条件下较为稳定。结论次黄嘌呤和肌苷的析出是影响肌苷口服液澄明度的主要原因,2%肌苷溶液在70℃和80℃条件下的降解符合一级动力学反应,在pH值13.5时的降解符合零级动力学反应。     

反相高效液相色谱法测定盐酸格拉司琼葡萄糖注射液的含量及有关物质

目的 建立盐酸格拉司琼葡萄糖注射液含量及有关物质的反相高效液相色谱(RP-HPLC)测定法.方法 采用C18色谱柱,磷酸盐缓冲液(pH值2.0)(取无水磷酸二氢钠15.6g溶解于900 ml水中,用磷酸调节pH值至2.0,加水稀释至1000 ml)-甲醇-四氢呋喃(75∶24∶ 1.1)为流动相,流速1.2 ml/min,检测波长300 nm.结果 盐酸格拉司琼与杂质A、B、C、D及5-羟甲基糠醛的分离度均符合要求,系统适用性良好,盐酸格拉司琼在0.4426 ～2.213 μg范围内线性关系良好,方法平均回收率为100.1％(相对标准偏差=0.26％).结论 该法简便、准确,可用于盐酸格拉司琼葡萄糖注射液的主药含量及有关物质测定.     

注射用卡络磺钠与注射用盐酸头孢替安的配伍稳定性考察

目的考察注射用卡络磺钠与注射用头孢替安在0．9％氯化钠注射液中的配伍稳定性。方法采用反相高效液相色谱法测定卡络磺钠与头孢替安在0．9％氯化钠注射液中配伍后8h内各时间点的含量,并测定pH值,观察配伍液的外观变化。结果卡络磺钠的平均回收率为99．5％,相对标准偏差（RSD）为0．73％;头孢替安的平均回收率为99．7％,RSD为0．90％。在室温[（20-4-1）℃]下0、1、2、3、4、5、6、8h时,配伍液外观、pH值及含量均无明显变化。配伍液外观均为橙红色澄明,无肉眼可见的气泡产生及沉淀生成。配伍液pH值分别为4．57、4．58、4．59、4．61、4．62、4．63、4．65、4．68,卡络磺钠含量分别为100．0％、99．5％、100．3％、99．8％、99．0％、99．5％、99．1％、99．0％,头孢替安含量分别为100．0％、100．6％、99．9％、99．5％、99．1％、98．9％、99．0％、98．8％。结论在室温[（204-1）℃]下,注射用卡络磺钠与注射用头孢替安在0．9％氯化钠注射液中8h内可以配伍使用。     

消旋四氢巴马汀对血压及外周组织去甲肾上腺素和肾上腺素含量的影响

消旋四氢巴马汀(THP)iv、ip和ig均可明显地降低麻醉大鼠的血压和减慢心率,THP 1.0、5.0、10.0mg·kg~(-1)椎动脉注射对麻醉兔血压和心率无明显影响,而以等剂量iv,则可引起降压,高压液相色谱-电化学检测法测定结果表明THP可明显减少大鼠心脏、主动脉、股动脉中NE和肾上腺中E含量,THP降压效应与血管中NE含量下降呈显著正相关,     

丹参酮ⅡA磺酸钠注射液配伍稳定性考察

目的考察丹参酮ⅡA磺酸钠注射液分别与果糖注射液、果糖氯化钠注射液、转化糖注射液的配伍稳定性。方法分别观察及测定30E条件下,6h内各配伍液的外观、PH值变化．并采用高效液相色谱法（HPLC）测定各配伍液中丹参酮ⅡA的含量变化。结果在30E条件下．丹参酮ⅡA磺酸钠注射液与果糖注射液等配伍后,6h内各配伍液的外观、PH值及丹参酮ⅡA的含量均无明显变化。结论丹参酮ⅡA磺酸钠注射液与果糖注射液等配伍6h内基本稳定。     

对注射用盐酸艾司洛尔与相关物质的含量测定及其稳定性考察

目的：建立自制的注射用盐酸艾司洛尔与相关物质的含量测定方法,并考察其稳定性。方法：制备样品,采用HPLC法测定盐酸艾司洛尔及相关物质的含量,并对制剂进行稳定性考察。色谱条件为ZorbaxRX-C18色谱柱（250mm×4.6mm,5μm）;流动相：甲醇-冰乙酸-0.14%的乙酸钠溶液（40：1：60）;检测波长：280nm;流速：1ml/min。结果：本品处方以甘露醇作为赋形剂,用盐酸或氢氧化钠溶液调节pH值为4.5～5.5。盐酸艾司洛尔在5.0～50.0μg/ml范围内线性关系良好（r=0.9997）,在加速试验6个月及长期稳定性试验24个月中主药及相关物质含量未见明显变化。结论：该制剂处方工艺可行,质量可控,稳定性良好。所建立的含量测定方法重复性好,专属性强,结果准确可靠。     

Antibiotic granules for reconstitution as syrups: product uniformity and stability dependent upon reconstitution procedure

The penicillin content and stability of diluted antibiotic syrups, prepared according to the manufacturers' recommendations and other, non-approved, methods have been investigated. Methods which involve portioning the granules before reconstitution are hazardous and may result in preparations which range from very little antibiotic content to a double strength preparation. The choice of diluent controls the stability of the preparation. Phenoxymethylpenicillin syrups become less stable as the sucrose content increases. This is not always true with ampicillin syrups where the system is more complex. Although syrups prepared according to the manufacturers' instructions are not always the most stable, the effect of different diluents on the stability of syrups, especially suspensions, suggests that syrups should always be reconstituted and diluted according to the directions provided with the product.