LC-QQQ-MS/MS分析苯磺酸氨氯地平中痕量苯磺酸酯类基因毒性杂质

摘要：目的 建立LC-QQQ-MS/MS分析测定苯磺酸氨氯地平中痕量苯磺酸酯类基因毒性杂质苯磺酸甲酯、苯磺酸乙酯、苯磺酸丙酯和苯磺酸异丙酯的检测方法。方法 采用Agilent Zorbax SB-C18（3.0mm×100mm,1.8μm）色谱柱,以水（含 5mMol?L-1甲酸铵和0.1%甲酸）和甲醇（含5mMol?L-1甲酸铵和0.1%甲酸）为流动相,梯度洗脱,流速0.4 mL?min-1,电喷雾离子化（ESI）,正离子模式下MRM采集。结果 苯磺酸甲酯定量限为20 ng?mL-1,苯磺酸乙酯、苯磺酸丙酯和苯磺酸异丙酯定量限为1 ng·mL-1;方法精密度良好,保留时间和峰面积RSD%均小于5%（n=10）;苯磺酸甲酯在20~1000ng·mL-1,苯磺酸乙酯、苯磺酸丙酯和苯磺酸异丙酯在1~1000ng?mL-1的浓度范围内呈良好的线性关系,r≥0.998;方法准确度良好,平均加标回收率（n=10）分别为99.77%、100.19%、94.21%和92.43%。5个不同厂家生产的苯磺酸氨氯地平中苯磺酸甲酯的含量均小于LOQ（8μg?g-1）,苯磺酸乙酯、苯磺酸丙酯和苯磺酸异丙酯的含量均小于LOQ（0.4μg?g-1）。结论 该方法可用于苯磺酸氨氯地平中痕量基因毒性杂质苯磺酸甲酯、苯磺酸乙酯、苯磺酸丙酯和苯磺酸异丙酯含量的检测分析。     

Lipid based nanocarriers: a translational perspective

Over the recent couple of decades, pharmaceutical field has embarked most phenomenal noteworthy achievements in the field of medications as well as drug delivery. The rise of Nanotechnology in this field has reformed the existing drug delivery for targeting, diagnostic, remedial applications and patient monitoring. The convincing usage of nanotechnology in the conveyance of medications that prompts an extension of novel lipid-based nanocarriers and non-liposomal systems has been discussed. Present review deals with the late advances and updates in lipidic nanocarriers, their formulation strategies, challenging aspects, stability profile, clinical applications alongside commercially available products and products under clinical trials. This exploration may give a complete idea viewing the lipid based nanocarriers as a promising choice for the formulation of pharmaceutical products, the challenges looked by the translational process of lipid-based nanocarriers and the combating methodologies to guarantee the headway of these nanocarriers from bench to bedside.     

预注法联合限时法缩短顺苯磺酸阿曲库铵起效时间疗效观察

目的：研究预注法联合限时法缩短顺苯磺酸阿曲库铵起效时间的效果。方法：成年择期手术全麻患者112例按入院先后顺序分为甲乙丙3组,3组患者均使用芬太尼4μg·kg-1和丙泊酚2 mg·kg^-1作为诱导药。甲组采用预注法联合限时法,患者先静注顺苯磺酸阿曲库铵20μg·kg-1,3 min后再先后注射诱导药和顺苯磺酸阿曲库铵80μg·kg-1;乙组采用预注法,患者先静注顺苯磺酸阿曲库铵100μg·kg-1,1.5 min后注入诱导药;丙组采用限时法,患者先后注入诱导药与顺苯磺酸阿曲库铵l00μg·kg-1。观察比较各组诱导前T1百分比,肌肉颤搐抑制90%和100%的时间、气管插管评级以及药品不良反应。结果：3组患者气管插管优秀率比较,差异无统计学意义（P〉0.05）。与甲、乙组比较,丙组诱导前不存在T1抑制,乙组（9.8±2.6）多于甲组（3.2±1.5）（P〈0.01）;达肌肉颤搐抑制90%与100%时间,丙组明显长于甲、乙两组（P〈0.01）。丙组不良反应发生率明显高于甲、乙两组（P〈0.05）。结论：应用预注法以及限时法,均可有效缩短顺苯磺酸阿曲库铵的起效时间,效果显著,且安全性高。     

气相色谱法测定苯磺阿曲库铵原料中的残留溶剂

目的:用毛细管柱气相色谱法建立苯磺阿曲库铵中残留溶剂(乙醚、丙酮、甲醇、二氯甲烷、乙腈、甲苯)的测定方法。方法:采用DM-Wax(30 m×0.53 mm,1.00μm)毛细管柱(固定相为键合交联聚乙二醇),以氮气为载气,FID检测器,采用程序升温,分流直接进样,外标法计算残留溶剂的含量。结果:在考察的浓度范围内呈现良好的线性关系(乙醚r=0.9997,丙酮r=0.9997,甲醇r=0.9996,二氯甲烷r=0.9996,乙腈r=0.9991,甲苯r=0.9997),平均回收率范围为97.4%～99.7%,理论塔板数均>7000,相邻的峰之间的分离度均>2,精密度、重复性RSD均<3%。结论:本方-法简单、结果准确、重现性好,可用于苯磺阿曲库铵中乙醚、丙酮、甲醇、二氯甲烷、乙腈、甲苯6种残留溶剂的同时测定。     

维库溴铵与苯磺阿曲库铵的肌松作用在阻塞性黄疸和肾衰患者手术时的应用

维库溴铵与苯磺阿曲库铵应用于肝肾功能正常者33例、末期肾衰病人26例、阻塞性黄疸病人20例。静注维库溴铵与苯磺阿曲库铵初剂量分别为0.1mg/kg和0.5mg/kg,每次追加剂量分别为0.05mg/kg和0.25mg/kg,术中用4个成串刺激(TOF)监测肌松程度。应用2药于肾衰组,除起效时间较其他2组明显缩短外,其他参数无差异,前者用于阻黄病人时,TOF在恢复过程中第4(T_4)与第1(T_1)个刺激反应强度之比(RTOF)0.25和恢复指数均有明显延长,提示有积蓄作用,使用时应慎重。     

HPLC测定卡肌宁注射液中阿曲库铵苯磺酸盐异构体及相关杂质

在InertsilODS柱上,以乙腈一氯化四丁基铵(TBAC)体系为流动相,HPLC法同时分离阿曲库铵苯磺酸盐异构体及相关杂质,考察了色谱填料及流动相中乙腈量、氯化四丁基铵浓度及pH值对色谱保留的影响。该法用于卡肌宁注射液的质量控制和稳定性的初步考察,取得满意效果。     

Spectrophotometric and HPLC Methods for Simultaneous Estimation of Amlodipine Besilate, Losartan Potassium and Hydrochlorothiazide in Tablets

Two UV-spectrophotometric and one reverse phase high performance liquid chromatography methods have been developed for the simultaneous estimation of amlodipine besilate, losartan potassium and hydrochlorothiazide in tablet dosage form. The first UV spectrophotometric method was a determination using the simultaneous equation method at 236.5, 254 and 271 nm over the concentration range 5-25, 10-50 and 5-25 μg/ml for amlodipine besilate, losartan potassium and hydrochlorothiazide, respectively. The second UV method was a determination using the area under curve method at 231.5-241.5, 249-259 and 266-276 nm over the concentration range of 5-25, 5-25 and 10-50 μg/ml for amlodipine besilate, hydrochlorothiazide and losartan potassium, respectively. In reverse phase high performance liquid chromatography analysis is carried out using 0.025 M phosphate buffer (pH 3.7):acetonitrile (57:43 v/v) as the mobile phase and Kromasil C18 (4.6 mm i.d×250 mm) column as stationery phase with detection wavelength of 232 nm linearity was obtained in the concentration range of 2-14, 20-140 and 5-40 μg/ml for amlodipine besilate, losartan potassium and hydrochlorothiazide, respectively. Both UV-spectrophotometric and reverse phase high performance liquid chromatography methods were statistically validated and can be used for analysis of combined dose tablet formulation containing amlodipine besilate, losartan potassium and hydrochlorothiazide.     

白芍总苷联合苯磺贝他斯汀治疗慢性荨麻疹疗效观察

目的评价白芍总苷联合苯磺贝他斯汀治疗慢性荨麻疹的临床疗效及安全性。方法将115例慢性荨麻疹患者随机分为2组,治疗组57例,给予口服苯磺贝他斯汀片10 mg,2次/d,同时联合白芍总苷胶囊,600 mg,3次/d;对照组58例,仅口服苯磺贝他斯汀片,方法同治疗组,2组疗程均为12周。记录不良反应。结果 2组患者治疗后症状积分均明显下降,于治疗后第8周及第12周时,2组症状积分相比,差异有统计学意义(均P0.05);疗程结束时,治疗组有效率为91.23%,对照组有效率为75.86%,治疗组明显高于对照组,差异有统计学意义(P0.05);治疗过程中均无严重不良反应发生;治疗组的复发率明显低于对照组(P0.05)。结论白芍总苷联合苯磺贝他斯汀治疗慢性荨麻疹安全有效,复发率低。     

Health-related quality of life assessed by the effect of bepotastine besilate in patients with pruritus: importance of emotions score in atopic dermatitis

The Skindex-16 questionnaire was recently developed as a measure of dermatological health-related quality of life (HRQoL), including symptoms, emotions and functional aspects. Bepotastine besilate is a selective histamine H(1) -receptor antagonist and a second-generation non-sedating antihistamine to treat various dermatological disorders. We assessed changes of the HRQoL instrument (Skindex-16) on patients with pruritus, including those with atopic dermatitis (AD) over bepotastine treatment period. The patients' personal assessment of the intensity of pruritus was determined using the Visual Analog Scale (VAS) for pruritus. Patients answered the Skindex-16 at baseline and at week 4. Forty-eight of 51 enrolled dermatological patients completed the Skindex-16. Of the 48 patients, 11 had AD and 37 had other conditions. Improvement in the clinical evaluation and VAS score was significant in all patients, the AD group and the other disorders group between baseline and week 4. Skindex-16 showed significantly lower scores for each of the three scales (symptoms, emotions and functioning) and the global score at baseline compared to that at week 4 in all patients and the other disorders. In contrast, there was a significant reduction in the emotions and global score among the AD patients. We found a significant correlation between falls in emotions score of Skindex-16 and falls in VAS scores for pruritus in the AD group. Bepotastine could be effective in the management of patients' HRQoL and useful in patients suffering with pruritus. We suggested that pruritus of AD patients could exert a stronger emotional effect due to the skin condition compared to the symptomatic or functional effects.     

Non-clinical pharmacology,pharmacokinetics, and safety findings for the antihistamine bepotastine besilate

Abstract

Scope:

The purpose of this review is to examine published non-clinical literature on the antihistamine bepotastine besilate, including pharmacokinetic and pharmacologic properties.