Interactions between a poorly soluble cationic drug and sodium dodecyl sulfate in dissolution medium and their impact on in vitro dissolution behavior

In the pharmaceutical industry, in vitro dissolution testing ofsolid oral dosage forms is a very important tool for drug development and quality control. However, ion-pairing interaction between the ionic drugand surfactants in dissolution medium often occurs, resulting in inconsistent and incomplete drug release. The aim of this study is toevaluate the effects ofsodium dodecyl sulfate (SDS) mediated medium onthe dissolution behaviors of a poorly soluble cationic drug (Drug B). The study was carried out by measuring solubility of Drug B substance and dissolution rate of Drug B product in media containing SDS.Desolubilization of Drug B substance was observed at pH 4.5 in the presence of SDS at concentrations below critical micelle concentration (CMC) which is attributed to the formation of an insoluble di-dodecyl sulfate salt between SDS and Drug B. This ion-pairing effect is less significant with increasing medium pH where Drug B is less ionized and CMC of SDS is lower. In medium at pH 4.5, dissolution of Drug B product was found incomplete with SDS concentration below CMC due to the desolubilization of Drug B substance. In media with SDS level above CMC, the dissolution rate is rather slower with higher inter-vessel variations compared to that obtained in pH 4.5 medium without SDS. The dissolution results demonstrate that the presence of SDS in medium generates unexpected irregular dissolution profiles for Drug B which are attributed to incompatible dissolution medium for this particular drug. Therefore, non-ionic surfactant was selected for Drug B product dissolution method and ion-pairing effect in SDS mediated medium should be evaluated when developing a dissolution method for any poorly soluble cationic drugs.     

Effects of vasoconstrictors used in local anesthesia upon isolated rat heart.

Some reports have demonstrated that the vasoconstrictor effect of catecholamines may be amplified by felypressin. Thus, the association of felypressin and epinephrine with local anesthetics may be indicated to achieve more effective vasoconstrictor actions with fewer collateral effects from both the anesthetic and the vasoconstrictor. This study aimed to characterize the effects of felypressin and associations of felypressin and epinephrine upon the contraction force and the cardiac rate of the isolated rat heart (n=20) perfused by Langendorff's method. The following solutions were utilized: epinephrine, 4.5nmol; felypressin at doses of 0.5, 1.6 and 5.5IU and associations of felypressin at the same doses with 4.5nmol epinephrine. Contraction force and cardiac rate were recorded at 15, 30, 60 and 120s after the administration of each solution, and before the administration, a control measurement (time 0) was taken. Felypressin at a dose of 0.5IU did not have any effect upon the heart, but the doses of 1.6 and 5.5IU decreases the cardiac rate and the contraction force, respectively. Epinephrine and all of the felypressin and epinephrine associations produced increases in these parameters. The association of 0.5IU felypressin and 4.5nmol epinephrine promoted a similar effect to that of epinephrine (4.5nmol) alone up to 120s. The association of 1.6IU felypressin and 4.5nmol epinephrine increases the contraction force up to 60s. After the administration of the association of 5.5IU felypressin and 4.5nmol epinephrine this increase was observed up to just 30s. The cardiac rate values obtained after the administration of the associations of 1.6 and 5.5IU felypressin with 4.5nmol epinephrine were lower than those seen after the use of 4.5nmol epinephrine alone.In this study it was observed that the association of felypressin with epinephrine decreased the effects of epinephrine which increases the cardiac rate and the contraction force in the isolated rat heart.     

阿苯达唑工作参照品的测定

目的建立测定阿苯达唑参照品含量的方法。方法用二极管阵列检测器优化检测条件,采用两种色谱条件,从对照品纯度与参照品归一两个方面测定。通过C18色谱柱反相分离,流动相分别用乙腈-水(磷酸调pH4.5)(55:45)和甲醇-水(磷酸调pH4.5)(65:35)测定阿苯达唑及相关物质的含量。结果阿苯达唑含量为99.8%。结论所建测定方法灵敏,能互相印证,结果准确可靠,可作为阿苯达唑工作参照品含量控制的定量方法。     

Simultaneous determination of some common food dyes in commercial products by digital image analysis

A simple and relatively fast image-analysis method using digital images, obtained with a flatbed scanner, has been described. The method was used for the simultaneous determination of four common food dyes, namely, carmoisine, brilliant blue, sunset yellow, and quinoline yellow, in binary mixtures in commercial products without a need for any prior separation steps. The results obtained were validated against a standard high-performance liquid chromatography method and a good agreement was obtained. The parameters affecting the experimental results were optimized. Under the optimal conditions, the method provided acceptable linear ranges (20–250 mg/L) with correlation coefficients higher than 0.998, suitable precision (relative standard deviation ≤ 4.5%), and limits of detection between 4.82 and 8.05 mg/L.     

亮菌甲素(假密环菌甲素)含量测定方法的研究

亮菌甲素(3-乙酰基-5-羟甲基-7-羟基香豆素,简称甲素)系一种新的香豆素类化合物。首先由假密环菌(Armillariella tabescens(Scop.ex Fr.)Sing.)的菌丝体中提取所得,现已化学合成。甲素经临床试用,证明对急性胆道感染有一定的疗效。本文对其含量测定方法进行了研究。     

梯度渗漉法提取丹参有效成分的工艺

目的对渗漉方法提取丹参中有效成分丹参酮IIA、丹酚酸B进行研究。方法采用回流法、一般渗漉法与梯度渗漉法分别进行提取,应用正交实验设计和单因素考察的方法对提取工艺进行筛选,以HPLC法测定的丹参酮IIA、丹酚酸B的含量评价两种方式的提取效果。结果最佳提取工艺为梯度渗漉法,最佳的提取工艺条件为:取丹参药材粗粉,用适量95%乙醇溶胀2.5h,装入渗漉器材,用95%乙醇浸渍24h后,以4.5mL/min的速度开始渗漉,收集8倍药材量的渗漉液,提取丹参酮类脂溶性成分;再用50%乙醇,以4.5mL/min的速度渗漉,收集10倍药材量的渗漉液,提取丹参酚酸类水溶性成分,与HPLC测量结果比较,丹参酮IIA和丹酚酸B的提取率较高。结论梯度渗漉法提取丹参有效成分的最佳提取方式与一般渗漉法比较,提取率较高,完全适合丹参中有效成分的提取。     

Quantitation of a novel metalloporphyrin drug in plasma by atomic absorption spectroscopy

A bioanalytical method to quantify cobalt mesoporphyrin (CoMP), a novel therapeutic agent, in plasma has been developed and validated. The approach involves atomic absorption spectroscopy to determine total cobalt in a sample and a back-calculation of the amount of compound present. Endogenous plasma cobalt concentrations were small ( <0.2 ng/ml(-1) Co in rat plasma) in comparison to the quantitation limit (4.5 ng/ml(-1) Co). The inter-day imprecision of the method was 10.0% relative standard deviation (RSD) and the inter-day bias was +/- 8.0% relative error (RE) over a standard curve range of 4.5- 45.0 ng/ml(-1) Co. Because it quantifies total cobalt, the method cannot differentiate between parent drug and metabolites, but negligible metabolism allows reliable estimates of the actual parent drug concentration. A correlation study between the atomic absorption method and 14C-radiometry demonstrated excellent agreement (r = 0.9868, slope = 1.041 +/- 0.028, intercept = 223.7 +/- 190.0) and further substantiated the accuracy of the methods. Methodology was successfully applied to a pharmacokinetic study of CoMP in rat, with pharmacokinetic parameter estimation. The elimination half-lives, after intra-muscular and subcutaneous administration, were 7.7 and 8.8 days, respectively.     

硝苯地平片剂溶出度的考察

目的考察不同生产企业生产的硝苯地平片剂的体外溶出度。方法分别以0.1 mol.L-1盐酸溶液、人工胃液(不含胃蛋白酶)、pH 4.5醋酸钠缓冲液、pH 6.8磷酸盐缓冲液和蒸馏水为溶出介质,采用紫外分光光度法检查;以质量分数为0.25%十二烷基硫酸钠为溶出介质,采用HPLC法检查,比较不同厂家硝苯地平片剂的体外溶出度。用相似因子法评价硝苯地平片剂在0.1 mol.L-1盐酸溶液、人工胃液(不含胃蛋白酶)、pH 4.5醋酸钠缓冲液、pH 6.8磷酸盐缓冲液和蒸馏水中的溶出行为。结果在质量分数为0.25%十二烷基硫酸钠溶液中,硝苯地平的溶出度在60 min均大于65%,而在其他溶出介质中的溶出度均达不到《英国药典》及《美国药典》中规定的标准。相似因子f2均在50~100之间。结论溶出介质的pH值对硝苯地平的溶出度没有影响。从整体来看,国产硝苯地平片剂的体外溶出行为与国外制剂相比有很大差距。     

高效液相色谱-串联质谱法测定血浆中熊去氧胆酸的浓度

目的：建立高效液相色谱-质谱联用的方法测定人血浆内的熊去氧胆酸浓度的方法。方法：采用Shimadzu VP-ODS(4．6 mm×150 mm,5μm)色谱柱；柱温25℃；流动相为(A)乙腈-水(含5 mmol·L~(-1)的乙酸铵)(35：65,V/V),(B)乙情；梯度程序为0～2min,A：B=94：6；2～4．5min,A：B= 80：20：4．5～7min,A：B=94：6；流速为1．0 mL·min~(-1)；通过液相串联质谱,电喷雾离子源(ESI),以选择反应监测(SRM)方式进行检测；离子极性监测负离子(-)；检测离子为熊去氧胆酸m/z 391．1 [M-H]~-→391．1[M-H]~-,盐酸西替利嗪(内标)m/z 387．1[M-H]~-→387．1[M-H]~-。结果：熊去氧胆酸的最低定量限为40．144μg·L~(-1),线性范围为40．14～12 043μg·L~(-1)(r=0．995)。结论：该方法简便、灵敏度高,可以用来进行熊去氧胆酸的人体药动学和生物等效性研究。     

气相色谱法测定托吡酯中有机溶剂的残留量

目的建立抗癫痫药托吡酯中残留有机溶剂的含量测定方法。方法用气相色谱仪,采用DB-Wax(30 m×0.32 mm,0.25μm)毛细管柱;分流比:30∶1;进样口温度:150℃;柱温:初始温度45℃保持6 min,以25℃.min-1的速度升至150℃,保持4.5min;FID检测器温度:275℃;载气:N2;载气流速:1.5 mL.min-1;进样量:1.0μL。结果各残留溶剂线性关系良好,相关系数均大于0.99,回收率均在90%～110%之间。结论该方法操作简单,重复性好,灵敏度高,适用于托吡酯中残留溶剂的含量测定。     

高效液相梯度洗脱法测定注射用别嘌醇钠中的有关物质

目的建立测定注射用别嘌醇钠有关物质的高效液相梯度洗脱法。方法采用ODS C18色谱柱(250 mm×6 mm,5μm),以1.25 g.L-1磷酸二氢钾-甲醇(体积比为90∶10~70∶30)为流动相进行梯度洗脱,柱温为30℃,流速为1.0 mL.min-1,检测波长为230 nm。结果在上述色谱条件下,5种杂质(1-5)能与别嘌醇得到有效分离,分离度大于1.5;检测限为4.5 ng,精密度良好(RSD为0.71%)。结论高效液相梯度洗脱法可用于测定注射用别嘌醇钠中的有关物质。     

HPLC法测定盐酸倍他司汀氯化钠注射液的含量

目的建立HPLC法测定盐酸倍他司汀氯化钠注射液中盐酸倍他司汀的含量。方法用C18柱为固定相,以pH4·5磷酸三乙胺缓冲液为流动相,检测波长为261nm。结果盐酸倍他司汀在20~100μg·ml-1浓度范围内呈良好的线性关系(r=0·9999),其平均回收率为100·2%,RSD为1·04%(n=5)。结论此方法简便、快速、准确。     

高效液相色谱法测定人尿中酮洛酸含量

目的建立以高效液相色谱法测定人尿中酮洛酸浓度的方法。方法色谱柱为Waters Sunfire C18,流动相为0.02mol·L-1磷酸二氢钾溶液-乙腈(70∶30,用磷酸调节pH值至4.5),检测波长为315nm,柱温为35℃,流速为1mL.min-1,进样量为20μL,保留时间为9.1min。结果人尿中酮洛酸浓度在0.1～10.0μg·mL-1范围内线性关系良好,日内和日间RSD<10%,最低定量限为0.1μg·mL-1。结论本法简便、快捷、灵敏,适用于酮洛酸人体药动学研究。     

高效液相色谱法测定福沙匹坦二甲葡胺对映异构体

目的：建立测定福沙匹坦二甲葡胺对映异构体的高效液相色谱方法。方法：用硅胶表面共价键合有直链淀粉-三（3,5-二甲苯基氨基甲酸酯）为填充剂（CHIRALPAK^®IA,250 mm×4.5 mm,5 μm）;以正己烷-无水乙醇（90∶10）为流动相;检测波长为210 nm;流速为1.0 mL·min^-1。结果：对照品浓度在1.03~15.47 μg·mL^-1范围内线性良好（r=0.999 8）,平均回收率为98.94%,RSD为0.63%,定量限浓度为1.77 μg·mL^-1,检测限浓度为0.531 μg·mL^-1。结论：本方法专属性强、准确度高,可用于福沙匹坦二甲葡胺对映异构体的质量控制。     

HPLC法测定盐酸法舒地尔注射液的含量

目的建立高效液相色谱法测定盐酸法舒地尔注射液含量的方法。方法采用Welch Ultimate XB-C8色谱柱(4.6 mm×250 mm,5μm),流动相为0.03 mol.L-1磷酸氢二铵溶液-乙腈=76:24(用磷酸调节pH值至4.5),检测波长为275 nm,流速为1.0 mL.min-1。结果盐酸法舒地尔在90.04～210.08μg.mL-1的浓度范围内线性关系(r=0.999 9)良好,平均回收率为99.87%,RSD为0.24%。结论本方法专属强、准确度高,可用于盐酸法舒地尔注射液的质量控制。     

复方虫草利湿益肾丸对小鼠虚喘证候模型的影响

目的观察复方虫草利湿益肾丸对小鼠虚喘证候模型的治疗作用。方法以木瓜蛋白酶肺气肿疾病模型联合糖皮质激素制作虚喘证候模型,用系列检测指标进行论证。结果复方虫草利湿益肾丸对虚喘证候模型用药治疗后,各剂量组动物的状态明显好转,其外观状态与空白对照组相似;本品9.0g.kg-1组能缓解氢化可的松造成的小鼠体质量下降(P<0.05);9.0和4.5g.kg-1组可明显提高虚喘证候模型小鼠体温(P<0.05);9.0和4.5g.kg-1组小鼠自主活动次数显著高于虚喘模型对照组(P<0.05～0.01),提示复方虫草利湿益肾丸具有改善小鼠虚喘证候模型体征作用。9.0和4.5g.kg-1组能明显延长虚喘证候模型小鼠低温游泳存活时间(P<0.05),提示复方虫草利湿益肾丸能明显增强虚喘证候模型小鼠耐寒耐疲劳能力;9.0,4.5和2.25g.kg-1组能使虚喘证候模型小鼠胸腺指数显著升高(P<0.01),明显改善虚喘证候模型小鼠胸腺萎缩状况。结论复方虫草利湿益肾丸对虚喘证候模型小鼠有明显的治疗作用。     

Alterations in the toxicity of cis-Dichlorodiammineplatinum-II and in tissue localization of platinum as a function of NaCl concentration in the vehicle of administration

The lethality to mice of the anticancer drug cis-dichlorodiammineplatinum-II (cisPt) was greatly reduced when the drug was dissolved in hyperonic (4.5%) NaCl relative to preparation in distilled water (DW). Concomitant administration of 4.5% NaCl and cisPt prepared in DW failed to protect mice against cisPt toxicity. When other chloride salts were used as vehicles, partial protection was observed and when NaI was used as a vehicle, nearly complete protection was obtained. Similarly in rats, toxicity was reduced with the hypertonic vehicle when lethality, clinical chemistry, or histopathology criteria were evaluated. In vitro and in vivo binding to plasma proteins was greater with the DW vehicle. Tissue Pt levels were less and decayed more rapidly with the hypertonic NaCl vehicle. Antitumor effectiveness of cisPt was not altered when 4.5% NaCl was utilized as the vehicle. A postulated explanation for these results is a shift in the cisPt aquation reaction due to the high concentration of chloride ions in the vehicle.     

Simultaneous determination of lidocaine hydrochloride, hydrocortisone and nystatin in a pharmaceutical preparation by RP-LC

A liquid chromatographic (LC) method was developed to analyze a formulation (mouthwash) containing lidocaine hydrochloride, hydrocortisone and nystatin. A single LC method with UV detection was developed. A Waters Symmetry C18 HPLC column (150 mm ×  4.6 mm, 5 μm) was used as stationary phase and the assay was performed with gradient elution using mobile phases containing methanol - 0.1 M NaH₂PO₄ with a pH that was previously adjusted to 4.5 with dilute phosphoric acid. The sample pretreatment was performed by treating the formulation with methanol followed by filtration. After method development, the influence of the different chromatographic parameters on the separation, the interference of other active compounds and excipients, linearity, accuracy, repeatability and intermediate precision were investigated. The method was shown to be selective, linear, accurate, precise and repeatable. Finally, the content of the compounds in the formulation was determined.     

A Comprehensive Study Demonstrating that P-glycoprotein Function is Directly Affected by Changes in pH: Implications for Intestinal pH and Effects on Drug Absorption

The purpose of this study was to investigate whether changes in the pH of the gastrointestinal tract can directly affect P-glycoprotein (P-gp) function. The effect of changes in extracellular pH on P-gp functionality was examined by testing colchicine (a nonionizable P-gp substrate) in bidirectional Caco-2 and MDR1–Madine Darby canine kidney (MDCK) cell permeability assays, in which the pH of the apical and basolateral chambers was varied. Reduction of the pH from 7.4 to 5.0 and 4.5 markedly increased the apical-to-basolateral flux of colchicine and reduced the basolateral-to-apical flux. The efflux ratio for colchicine was reduced to 1.2 at pH 4.5, compared with values greater than 20 that were measured in the pH range of 5.5–7.4. A similar result was obtained when MDR1–MDCK cells were used in the bidirectional permeability studies. Other nonionizable P-gp substrates (digoxin, dexamethasone, paclitaxel, and etoposide) responded to acidic pH (4.5) in a manner similar to colchicine. Reduced P-gp ATPase activity is a reason for the diminished P-gp function observed at pH 4.5. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:4258–4268, 2011     

RP-HPLC法同时测定乙肝舒康胶囊中没食子酸和丹参素含量

目的建立同时测定乙肝舒康胶囊中没食子酸和丹参素的高效液相色谱法。方法采用Hy-persil C18色谱柱(200.0 mm×4.6 mm,5μm),以甲醇-体积分数为0.5%的冰醋酸溶液(体积比为4∶96)为流动相,流速:1.0 mL.min-1,检测波长:280 nm。结果没食子酸和丹参素的线性分别为4.5~90.0 mg.L-1(r=0.999 9)和7.5~150.0 mg.L-1(r=0.9994),平均回收率分别为99.1%和100.2%,RSD分别为2.2%和2.4%。