腺苷钴胺的光学稳定性研究

目的研究腺苷钴胺在可见光照条件下的光学稳定性。方法分别在400,450,500,550,600,650和700nm波长下以及50,100,200,300,400和500lx光照强度下,对腺苷钴胺对照品溶液进行40min光照实验,采用HPLC法测定光照射后的腺苷钴胺溶液。结果腺苷钴胺光降解率最小的光照波长为600nm,光照强度为50lx。结论明确腺苷钴胺的光降解率最低的照射波长和光照强度,可有效控制腺苷钴胺的光降解率,为避光措施提供科学依据。     

光和温度对输液中腺苷钴胺稳定性的影响

目的:研究输液中腺苷钴胺在光和热同时作用下的稳定性.方法:于不同浓度(500mg·L-1,50 mg·L-1)、不同温度(25℃、35℃)、不同光照度(55±5 Lx、遮光)条件下,考察腺苷钴胺在注射用水、氯化钠、葡萄糖输液中60 min内外观色泽,澄明度,pH,含量变化情况.结果:在室温室内自然光照射下,配伍后溶液中pH值均不同程度升高,腺苷钴胺含量明显下降.在遮光条件下,配伍后溶液中pH值几无变化,含量略有下降.结论:注射用腺苷钴胺溶解后,应立即使用,注意避光.     

腺苷钴胺水溶液的光降解动力学研究

目的：考察腺苷钴胺水溶液的光降解动力学特征。方法：运用HPLC法测定水溶液中腺苷钴胺含量及有关物质。考察样品浓度、光强度、温度、pH对腺苷钴胺水溶液光稳定性的影响。结果：经线性拟合对比分析,腺苷钴胺溶液的光降解反应级数为n=1,腺苷钴胺溶液对光极敏感,在pH2．5—3．5的溶液中相对稳定,腺苷钴胺溶液的光降解随样品浓度的降低、光强度的升高而增加,恒温避光加速试验中腺苷钴胺溶液的光降解并不随温度的升高而升高,但恒温光照加速试验中温度的升高明显加速腺苷钴胺溶液的光降解。结论：腺苷钴胺溶液光降解属近似一级动力学过程,光降解速率受溶液pH影响显著,热可加速腺苷钴胺溶液的光降解。     

腺苷钴胺凝胶中腺苷钴胺的含量测定

目的 采用高效液相色谱(HPLC)法测定腺苷钴胺凝胶中的腺苷钴胺含量. 方法色谱柱为Uitimate Column XB C₁₈(4.6 mm×250 mm,5 μm),以0.05 mol.L^-1磷酸二氢钾溶液(用磷酸调节pH为3.2)-乙腈(83:17)为流动相;柱温:35 ℃;进样量:10 μL;流速:1.0 mL.min^-1,检测波长:260 nm. 结果 腺苷钴胺在10～50 μg.mL^-1范围内线性关系良好(r＝0.999 9),平均回收率为99.49%,RSD为0.60%(n＝9). 结论 该方法专属性强、准确,可用于测定腺苷钴胺凝胶的含量.     

高效液相色谱法测定腺苷钴胺片的有关物质

摘要：目的:建立高效液相色谱法测定腺苷钴胺片有关物质的方法。方法:色谱柱：Agilent ZORBAX SB C18柱（250 mm×4.6 mm, 5μm）;流动相：乙腈-0.02 mol·L-1醋酸铵溶液（用醋酸调节pH至4.0）（15∶85）;流速：1.0 ml·min-1;柱温：35℃;检测波长：260 nm;进样量20μl。结果:在该色谱条件下,腺苷钴胺峰、羟钴胺素峰、氰钴胺素峰及其他单个杂质峰均能有效分离。杂质氰钴胺素和杂质羟钴胺素的浓度分别在0.124～2.35μg·ml-1（r=0.999 5）、0.207～5.08μg·ml-1（r=0.999 6）范围内与峰面积成良好的线性关系。平均回收率分别为99.2%,99.4%,RSD分别为0.5%和0.3%（n=9）。10批样品中,羟钴胺素均有检出,6批样品中有杂质氰钴胺素检出;其他单个未知杂质含量在0.3%～0.5%之间。杂质总和在0.6%～0.9%之间。结论:经方法学验证,本方法可适用于腺苷钴胺片有关物质的测定。     

高效液相色谱法测定注射用腺苷钴胺中羟钴胺素并比较不同生产企业样品质量

目的建立HPLC法测定注射用腺苷钴胺中羟钴胺素的含量,并比较国内不同生产企业样品质量。方法采用高效液相色谱梯度洗脱法,色谱柱为资生堂MG-ⅡC_(18)柱(250 mm×4.6 mm,5μm),流动相A:0.05 mol·mL~(-1)磷酸二氢钾溶液(磷酸调pH值至3.2)-乙腈(90∶10);流动相B:乙腈-水(80∶20);流速为1.0 mL·min~(-1),检测波长为260 nm,柱温为35℃,进样量为20μL。结果羟钴胺素检测质量浓度线性范围为0.4~8.0μg·mL~(-1)(r=1.000);检测限为2.2 ng;精密度、重复性、稳定性试验结果 RSD分别为0.69%、2.3%和2.0%;平均加样回收率在103.3%~104.0%(RSD<1.0%,n=3)。92批次样品的羟钴胺素含量均值在0.02%~1.58%,均值0.34%;不同生产企业样品中的羟钴胺素的量存在差异。结论该方法准确、简便、专属性强,可用于注射用腺苷钴胺中羟钴胺素的测定和比较,对产品质量评价更有区分力。     

HPLC法测定注射用环磷腺苷葡胺中葡甲胺含量

目的:建立HPLC法测定注射用环磷腺苷葡胺中葡甲胺的含量。方法:XDB-C₁₈柱(4.6 mm×250 mm,5μm),流动相为庚烷磺酸钠缓冲液-乙腈(95:5),流量为1.0 mL·min^-1,检测波长为195 nm。结果:葡甲胺在0.25~5 mg·mL^-1浓度范围内线性回归方程的相关系数为0.9999;平均回收率为100.1%,其RSD为0.42%。结论:本法操作简便,结果准确,可用于注射用环磷腺苷葡胺中葡甲胺的含量测定。     

正交设计试验优选腺苷钴胺片处方

目的:优化腺苷钴胺片的处方组成。方法:以辅料中的羧甲基淀粉钠、微粉硅胶、硬脂酸镁用量为因素,以溶出度为指标,采用L9(34)正交设计试验优化腺苷钴胺片处方(每片含腺苷钴胺0.25 mg),对所制腺苷钴胺片进行验证试验(30 min溶出度、羟钴胺素在460 nm与352 nm处吸光度比值、崩解时限和含量),并考察制剂的加速稳定性。结果:辅料中影响腺苷钴胺片溶出度的主要因素是羧甲基淀粉钠;最优处方(10 000片)为羧甲基淀粉钠18 g,微粉硅胶1.8 g,硬脂酸镁3 g;所制片剂的30 min溶出度为97%⁹9%,羟钴胺素的吸光度比值均为0.93,崩解时间为999%,羟钴胺素的吸光度比值均为0.93,崩解时间为9¹0 min,含量为99.3%10 min,含量为99.3%⁹9.7%,6个月的加速试验结果与0个月时比较无明显变化。结论:成功制得各项指标符合《中国药典》要求的腺苷钴胺片。     

注射用辅酶A、三磷酸腺苷二钠及肌苷注射液配伍稳定性考察

摘 要 目的：考察注射用辅酶A、三磷酸腺苷二钠注射液及肌苷注射液在5%葡萄糖注射液中的配伍稳定性。 方法: 在室温条件下,模拟临床用药方法,配制3种药物与5%葡萄糖注射液的配伍溶液,采用HPLC法测定辅酶A、三磷酸腺苷二钠和肌苷的含量及有关物质变化情况,同时考察配伍溶液的外观、pH和不溶性微粒的变化情况。结果: 室温下4 h内,配伍溶液的外观、pH、不溶性微粒、各药物含量及有关物质均无明显变化;24 h后,配伍溶液出现浑浊絮状物,pH、不溶性微粒、含量及有关物质均明显发生变化。结论:在室温条件下,注射用辅酶A、三磷酸腺苷二钠注射液及肌苷注射液在5%葡萄糖注射液中的配伍溶液应于4 h内使用完。     

高效液相色谱法测定腺苷钴胺片中的羟钴胺素含量

目的建立高效液相色谱法测定腺苷钴胺片中的羟钴胺素含量。方法采用DIKMA C8色谱柱(150mm×4.6 mm,5μm),流动相为柠檬酸-磷酸氢二钠缓冲液(pH=4.0)-甲醇(80:20),柱温为35℃,流速为1.0 mL·min-1,检测波长为351 nm。结果羟钴胺素在1.0²0.0μg·mL-1与峰面积呈良好线性关系(r=0.999 7),低、中、高浓度平均回收率分别为99.0%、100.2%、100.0%,RSD分别为0.17%、0.21%、0.23%(n=3),检出限为4.0 ng,日内、日间精密度RSD分别为0.58%和0.69%(n=6)。结论该方法灵敏、准确,专属性强,可作为腺苷钴胺片中的羟钴胺素含量测定。     

In-Use Photostability Practice and Regulatory Evaluation for Pharmaceutical Products in an Age of Light-Emitting Diode Light Sources

This article describes how the increased use of energy-efficient solid-state light sources (e.g., light-emitting diode [LED]-based illumination) in hospitals, pharmacies, and at home can help alleviate concerns of photodegradation for pharmaceuticals. LED light sources, unlike fluorescent ones, do not have spurious spectral contributions <400 nm. Because photostability is primarily evaluated in the International Council of Harmonization Q1B tests with older fluorescent bulb standards (International Organization for Standardization 10977), the amount of photodegradation observed can over-predict what happens in reality, as products are increasingly being stored and used in environments fitted with LED bulbs. Because photodegradation is premised on light absorption by a compound of interest (or a photosensitizer), one can use the overlap between the spectral distribution of a light source and the absorption spectra of a given compound to estimate if photodegradation is a possibility. Based on the absorption spectra of a sample of 150 pharmaceutical compounds in development, only 15% would meet the required overlap to be a candidate to undergo direct photodegradation in the presence of LED lights, against a baseline of 55% of compounds that would, when considering regular fluorescent lights. Biological drug products such as peptides and monoclonal antibodies are also expected to benefit from the use of more efficient solid-state lighting.     

Particular features of photolabile substances in tablets

Nifedipine and molsidomine tablets are extremely photolabile drug preparations, even at cool room light. Compared to solutions the light spectrum responsible for photodegradation is moved towards the long-wavelength range corresponding to the bathochromic shift of light absorption in the solid state. In the case of nifedipine tablets light up to 500 nm, especially the range between 400-420 nm, is degrading. Molsidomine tablets are affected only by ultraviolet light, but not by visible light. In both cases light penetrates less than 1 mm into the tablets. For nifedipine tablets the exact penetration depth could be determined due to the discolouration of the drug substance upon irradiation. It varied from 360 microm to 880 microm depending on the drug content. Since the decomposition products of nifedipine act as photostabilizers by spectral overlay, light penetration and photodegradation in nifedipine tablets are limited. The formation of gaseous and liquid decomposition products in molsidomine tablets enhances photodegradation. Changes of the tablet structure as well as dissolution and migration processes are discussed. Furthermore the degradation products donot photostabilize the drug substance due to the missing light absorption above 300 nm.     

脱镁叶绿一酸a荧光特性研究

目的:研究中药蚕砂中脱镁叶绿一酸a的荧光性质。方法:采用丙酮提取,Al2O3柱层析和乙醚萃取自蚕砂中分离脱镁叶绿一酸a,采用荧光扫描确定其激发波长和发射波长,考察pH值、温度及光照时间对其荧光强度的影响。结果:脱镁叶绿一酸a的激发波长和发射波长分别为665和675 nm。pH碱性、提高温度可降低其荧光强度,光照则可提高其荧光强度。结论:脱镁叶绿一酸a在中性、酸性和低温条件下稳定,光照可加强其荧光效应。     

紫外系数倍率法测定雷尼替丁血药浓度

目的 :测定雷尼替丁血药浓度。方法 :采用紫外系数倍率法 ,以甲醇作对照液 ,在波长200nm～400nm范围内扫描 ,选定λ1=324nm、λ2=358nm ,绘制工作曲线。结果 :口服雷尼替丁血药浓度有明显的双峰现象。结论 :本方法简便 ,适宜于基层单位进行血药浓度检测。     

Phase IV randomized preference study in patients eligible for calcium and vitamin D supplementation

Introduction/objectives: Preference for supplement formulation helps determine an individual’s adherence to long-term medication and can improve clinical benefit for chronic illnesses such as osteoporosis. This study compared the preference, acceptability and tolerability of a reformulation of Calcichew D3¹ 500?mg/400?IU and Calcichew D3 500?mg/800?IU (Takeda UK Ltd, Wobrun Green, UK) with Adcal-D3² 500?mg/400?IU (ProStrakan Ltd, Galashiels, UK) and Kalcipos-D 500?mg/800?IU (Meda Pharmaceuticals Ltd, Bishop's Stortford, UK), respectively.

Method: This phase IV, randomized, open-label, two-period, cross-over study was conducted at nine sites in the UK and Germany. Eligible subjects (≥65 years requiring calcium/vitamin D supplementation for prevention/treatment of deficiencies, or ≥18 years requiring supplementation as an adjunct to osteoporosis treatment) were randomly assigned to one of two 2 week treatment sequences – Group 1: Calcichew D3 500/400 then Adcal-D3 500/400 (or vice versa), or Group 2: Calcichew D3 500/800 then Kalcipos-D 500/800 (or vice versa). After each treatment period, patients rated the treatment for acceptability using 100?mm visual analogue scales. After the second treatment period, patients indicated their treatment preference. The primary endpoint, the percentage of patients with a preference for each treatment, was analyzed with a logistic regression model.

Results: Two hundred and seventy-six patients were randomly assigned by treatment sequence, 138 to each group. Preference questionnaires among patients who preferred Calcichew or comparator revealed the odds for patients preferring Calcichew 500/400 (77.6%) over Adcal-D3 was 3.46 ([95% CI 2.24, 5.36], p?<?0.001) in Group 1, and Calcichew D3 500/800 (63.2%) over Kalcipos-D was 1.72 ([1.19, 2.47], p?=?0.004) in Group 2. Adverse events were mostly gastrointestinal and were comparable between groups. The new formulation of Calcichew D3 is acceptable and consistent with its known tolerability profile.

Conclusions: In this short-term 30?day study, patients preferred Calcichew D3 500/400 and Calcichew D3 500/800 over respective comparators. A trend towards better compliance with Calcichew D3 preference observed in Group 1 warrants a longer term study to identify treatment compliance.

Trial registration: Clinicaltrials.gov: NCT02457247.     

巴洛沙星胃漂浮缓释片的制备及体外释放

以体外漂浮性能和释放度为指标优化巴洛沙星胃漂浮缓释片的处方。结果表明,每片用量HPMCK100M为120mg、碳酸氢钠为200mg和羧甲淀粉钠为100mg的片剂能在1min内起漂,持续漂浮时间达8．2h,8h累积释放率达90％。按优化处方制备的片荆在高温（60℃）、强光（4500h）下贮存10d,均保持稳定,高温（相对湿度75％）条件下有吸湿现象。     

连翘苷检测波长的研究

目的:为选择连翘苷的最佳测定波长.方法:采用岛津公司的LC-10ADVP泵;SPD-M10AVP二极管阵列检测器;CLASS-VP LC色谱工作站,以乙腈-0.1%磷酸(24:76)为流动相,对4份连翘药材供试品,分别以三个通道在205、228、277nm波长处,进行测定.结果:4批样品在三波长处的测定结果无差异,RSD分别为0.72%、1.0%、0.55%、0.57%.讨论:三波长均可作为连翘的测定波长,205nm波长检测最灵敏,为228nm的约3.7倍,为277nm的约11.26倍.为不同连翘制剂的定量测定提供了参考依据.     

Functionality and health-status benefits associated with reduction of osteoarthritis pain

ABSTRACT

Objective: To evaluate the association between pain intensity improvement and improvements in functionality and health status in patients with chronic osteoarthritis pain of the hip or knee.

Methods: Data were obtained from a 12-week, randomized, double-blind, placebo-controlled study of tramadol ER 100?mg, 200?mg, 300?mg, or 400?mg once daily. Patients reported pain intensity with a 100-mm visual analog scale (0?=?no pain, 100?=?extreme pain) and functionality and health status with the disease-specific Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire and the generic Short-Form-36 Health Survey (SF?36). Pain intensity improvement from baseline was categorized as <?0%, 0–14%, 15–29%, 30–49%, 50–69%, and ≥?70%, and mean changes in WOMAC and SF?36 scores were determined for patients in each category.

Results: A total of 1011 patients received placebo (n?=?205) or tramadol ER 100?mg (n?=?202), 200?mg (n?=?201), 300?mg (n?=?201), or 400?mg (n?=?202). The degree of pain intensity improvement was correlated with the degree of improvement in WOMAC and SF?36 scores; as little as 15% reduction of pain intensity was associated with notable improvements in function and health status. Potential limitations included the lack of established thresholds to assess clinically meaningful changes in these outcomes.

Conclusions: Pain intensity improvement is associated with corresponding improvements in function and health status. While large improvements in pain intensity are associated with large improvements in health status and functionality, modest pain reductions are also associated with improvement of certain health status parameters.