HPLC法测定甲砜霉素胶囊含量

甲砜霉素胶囊为《中国药典》2000年版收载的抗生素类药品,现行的《美国药典》和《英国药典》中均未收载。《中国药典》采用的含量测定方法为加乙醇溶解,加50%的氢氧化钾溶液加热回流提取4小时后,用硝酸银滴定液进行电位滴定测定含量。该方法专属性不强,操作繁琐费时,干扰因素较多,容易产生较大的误差,且常用硝酸银滴定液不利于环境保护。本文采用分离分析的反相高效液相色谱法测定甲砜霉素胶囊的含量,操作简便,结果准确,提高了测定的效率。1.仪器与试剂惠普HP1100高效液相色谱仪;甲砜霉素对照品(中检所下发);国内3个厂家的甲砜霉素胶囊;甲…     

甲砜霉素胶囊含量测定方法的改进

目的:改进甲砜霉素胶囊的含量测定方法.方法:采用高效液相色谱法.色谱柱为Kromasil C18柱(150×4.6mm,5μm);流动相为:水-甲醇-冰醋酸(55:45:0.1);流速:1.0ml/min;检测波长273nm;柱温:室温;结果:甲砜霉素在1.0～10.0μg范围内具有良好的线性关系,平均回收率为100.2%,RSD=0.25%.结论:该法可用于甲砜霉素胶囊中的甲砜霉素含量测定.     

甲砜霉素β-环糊精包合物的研制

目的：增加甲砚霉素的溶解度和溶出度,提高药物在体内的生物利用度。方法：采用共沉淀法制备甲砜霉素β－环糊精包合物,以折光率控制包合工艺,用紫外光谱法及相溶解度图法进行鉴定,并考察其性质。结果：甲砜霉素β－环糊精包合物可以提高甲砜霉素的溶解度２．８４倍,３０ｍｉｎ的溶出度由７．３７％提高到３５．０２％。结论：甲砜毒素与β－环糊精能形成包合物,且能显著提高其溶解度和溶出速度。     

克拉霉素胶囊处方的优选

目的：为选择克拉霉素胶囊的最佳处方进行研究。方法：通过正交试验设计，以Td值为指标，优选出克拉霉素胶囊的最佳处方组成为每粒含克拉霉素0．25克，微晶纤维素0．075克，优质羧甲基淀粉钠0．015克。结果：经过实验测定，计算平均回收率为100．37％，RSD为0．67％(n=6)。结论：新配方胶囊的溶出度显著优于原产品，且该方法简便，值得推广。     

用HPLC法测定芪归生血胶囊中黄芪甲苷的含量

目的：建立芪归生血胶囊中黄芪甲苷（astragaloside Ⅳ）含量测定的HPLC法。方法：采用Hypersil C18柱（250mm×4．6mm，5μm），以乙腈-水（38：62）为流动相，流速为1．0mL／min，检测波长为203nm，柱温为25℃。结果：黄芪甲苷线性范围为0．0403～0．3628mg／mL。平均加样回收率为97．5％，RSD为1．1％（n=5）。精密度、稳定性和重现性实验结果均符合方法学要求。结论：本方法灵敏、准确，重复性好，可用于芪归生血胶囊中黄芪甲苷的含量测定。     

薄层扫描法测定安宫宁胶囊中千层纸甲素A的含量

目的：建立安宫宁胶囊中千层纸甲素A的含量测定方法。方法：测定波长λS＝315nm，参比波长λR＝360nm，展开剂为苯－甲醇－冰醋酸（95：5：0．2），结果：千层纸甲素A的平均回收率为96．96％，RSD＝2．1％，结论：该方法简便，快速，准确。可用于安宫宁胶囊的质量控制。     

甲砜霉素胶囊在健康人体药动学及生物等效性研究

目的:研究甲砜霉素胶囊在健康受试者体内的药动学过程及其人体生物等效性。方法:18例健康男性受试者用随机交叉给药方案,分别单次口服甲砜霉素胶囊试验药和参比药0．5 g,用HPLC分析方法对血药浓度进行测定,评价2种制剂的生物等效性。结果:试验与参比甲砜霉素胶囊的主要药动学参数AUC_(0-t)分别为(34．91±5．33)和(33．73±6．09)mg·h·L~(-1);AUC_(0-∞)分别为(37．00±5．74)和(35．64±6．50)mg·h·L~(-1);C_(max)分别为(6．84±1．25)和(6．48±1．58)mg·L~(-1);T_(max)分别为(1．75±0．68)和(1．96±0．78)h;t_(1/2)分别为(3．66±0．55)和(3．69±0．68)h。甲砜霉素胶囊的相对生物利用度为(105．32±39．75)%。结论:甲砜霉素胶囊试验药和参比药的AUC,C_(max)经方差分析和双单侧t-检验表明:2种制剂生物等效;T_(max)经非参数法检验,表明2种制剂无显著性差别(P＞0．05)。     

甲砜霉素胶囊人体生物等效性研究

目的:进行试验制剂甲砜霉素胶囊与参比制剂市售甲砜霉素胶囊生物等效性研究。方法:男性健康志愿者20名,随机分为2组,分别交叉单剂服用试验制剂或参比制剂甲砜霉素胶囊500mg,采用高效液相色谱法测定甲砜霉素经时血药浓度,计算药动学参数,评价2制剂的生物等效性。结果:试验制剂和参比制剂主要药动学参数t1/2为(3.7±s0.5)h和(3.1±0.6)h,tmax为(2.0±0.3)h和(2.0±0.3)h,cmax为(2.3±0.6)mg·L-1和(2.3±0.5)mg·L-1,AUC0～12为(9.0±1.4)mg·h·L-1和(9.0±1.6)mg·h·L-1,AUC0～∞为(9.8±1.8)mg·h·L-1和(9.8±1.6)mg·h·L-1。试验制剂甲砜霉素胶囊相对生物利用度(F)为(101±6)%。结论:甲砜霉素胶囊试验制剂和参比制剂为生物等效制剂。     

HPLC法测定头孢氨苄甲氧苄啶胶囊含量的方法改进

目的以HPLC法同时测定复方头孢氨苄甲氧苄啶胶囊中头孢氨苄与甲氧苄啶的含量。方法以0．02mol·L^-1磷酸溶液（用20％氢氧化钠调节pH值至3．5±0．05）-乙腈（85：15）为流动相,检测波长为235nm。结果头孢氨苄在10．00～90．00）μg·mL^-1、甲氧苄啶在2．00～18．00μg·mL^-1。范围内,峰面积与其浓度呈良好线性关系;头孢氨苄平均回收率为100．0％、RSD为0．15％;甲氧苄啶平均回收率为100．1％、RSD为0．19％。结论以本文中采用的流动相,对头孢氨苄甲氧苄啶胶囊进行测定,结果头孢氨苄、甲氧苄啶两组分分离度较好,峰形对称,结果准确;本法为测定头孢氨苄甲氧苄啶胶囊的含量提供了一种新的选择。     

HPLC法测定注射用盐酸甲砜霉素甘氨酸酯的有关物质和含量

目的建立一种准确快速检测注射用盐酸甲砜霉素甘氨酸酯有关物质和含量的高效液相色谱法。方法用十八烷基硅烷键合硅胶为填充剂;以甲醇-0.05mol/L的磷酸二氢钾溶液-三乙胺（20：80：0.05）用磷酸调节pH至3.0为流动相;检测波长为226nm。结果选用的方法能有效检测注射用盐酸甲砜霉素甘氨酸酯的含量和有关物质。结论本方法测定注射用盐酸甲砜霉素甘氨酸酯含量灵敏度高、专属性强、线性范围宽、方法回收率好;测定其有关物质,各杂质峰与主成分峰分离度较好,能保证各杂质有效检出,完全能够达到质量控制的要求。     

HPLC测定罗红霉素软胶囊的溶出度

目的 采用HPLC测定罗红霉素软胶囊的溶出度。方法 以醋酸盐缓冲液(pH 5.5)为溶出介质,桨法,转速为100 r·min^-1,60 min时取样,取样后采用HPLC测定。结果 罗红霉素在0.02~ 0.2 mg·mL^-1内呈良好的线性关系(r=0.999 9),罗红霉素软胶囊的平均回收率为100.1％(RSD=0.6%),溶出液稳定,3批软胶囊在60 min时平均溶出度均在75%以上并且有较好的均一性。结论 该法可用于罗红霉素软胶囊溶出度的测定。     

Dose proportionality of stavudine in hiv seropositive asymptomatic subjects: Application to bioequivalence assessment of various capsule formulations

The dose proportionality and bioequivalence of the capsule formulations used in clinical trials and the proposed commercial formulations of stavudine were assessed in an openlabel, single-dose, randomized four-way crossover study in 16 asymptomatic HIV-infected males. One capsule of stavudine (5, 10, 20, or 40 mg) was administered orally to each subject in each of the four treatment periods. Serial blood samples were collected for 10 h after each dose and the plasma was assayed for intact stavudine by a validated radioimmunoassay method. The plasma concentration-time data were subjected to noncompartmental pharmacokinetic analysis. For doses ranging from 5 to 40 mg, mean C_max and AUC_0-∞ values were in the range of 110.36–889.34 ng mL^?1 and 246.46–1945.97 h ng mL^?1 respectively. The mean C_max and AUC_0-∞ of stavudine increased in a dose-proportional manner. Irrespective of the dose, mean C_max values were observed at a median t_max of 0.75 h or less. Mean t_1/2 values were 1.97, 1.77, 1.67 and 1.66 h for the 5, 10, 20, and 40 mg capsules, respectively. For bioequivalence assessment, C_max and AUC_0-∞ values were normalized to the 10 mg dose since these parameters were dose proportional. The 10 mg capsule formulation used in phase-3 clinical trials was chosen as the reference. The relative bioavailability estimates and 90% confidence limits for the dose-normalized C_max values with the 10 mg capsule as the reference were 86% (76%, 96%), 99% (88%, 110%), and 90% (80%, 100%) for the 5, 20, and 40 mg capsules, respectively. The differences in the point estimates of the dose-normalized AUC_0-∞ values for the 5, 20, and 40 mg capsules relative to the 10 mg phase-3 capsule were 1% or less, and the 90% confidence limits were all within 95–106%. These results indicate that stavudine exhibits linear pharmacokinetics and that the 5, 10, 20, and 40 mg capsules of stavudine are bioequivalent.     

伏立康唑胶囊人体药动学及相对生物利用度研究

目的 研究健康受试者口服伏立康唑胶囊的药动学和相对生物利用度。方法 20名健康受试者随机服用伏立康唑受试胶囊剂和参比片剂各100 mg,用HPLC-MS/MS测定血浆中伏立康唑的浓度。结果 主要药动学参数,伏立康唑受试制剂与参比制剂的T_max分别为(0.75±0.15)和(0.84±0.25)h,C_max分别为(605.4±136.6)和(595.2±134.7)ng·mL^-1;t_1/2分别为(4.91±1.44)和(5.06±2.06)h,AUC_0-15分别为(1737.6±325.1)和(1750.6±352.8)ng·h·mL^-1。受试制剂与参比制剂的AUC_0-15和C_max经双单侧t检验,T_max经非参数检验,差异均无统计学意义。结论 统计学结果表明,2种制剂生物等效。     

单剂量口服茶碱缓释胶囊的人体生物等效性评价

目的选择12名男性健康志愿者,进行单剂量口服茶碱缓释胶囊的人体生物等效性评价。方法采用反相高效液相色谱法,以紫外273nm为检测波长,测定了单剂量口服200mg国产茶碱缓释胶囊受试药品在健康人体内的茶碱浓度,并与进口茶碱缓释胶囊参比药品进行对照。结果茶碱缓释胶囊的体内动态过程呈一级吸收的一房室开放模型,国产受试药品和进口参比药品的Cmax分别为(5.12±0.74)mg/L和(5.14±0.63)mg/L,tmax分别为(5.4±1.0)h和(5.3±1.1)h,MRT分别为(17.79±1.48)h和(17.61±1.78)h,t1/2分别为(10.55±0.75)h和(10.59±1.10)h,AUC0-36分别为(85.33±10.56)mg*h/L和(86.26±8.80)mg*h/L。结论以体内茶碱AUC0-36数值表征的国产茶碱缓释胶囊的相对生物利用度为(98.9±6.4)%;选择Cmax、AUC0-36和AUC0-∞进行三因素方差分析与双单侧t检验,结果表明国产茶碱缓释胶囊和进口茶碱缓释胶囊两种制剂具有生物等效性。     

Serum and lung levels of thiamphenicol after administration of its glycinate N-acetylcysteinate ester in experimentally infected guinea pigs

Thiamphenicol is an analogue of chloramphenicol and is characterised by a broad spectrum of action. In this study, serum and lung levels of thiamphenicol (TAP) were studied in infected guinea pigs after the administration of thiamphenicol glycinate N-acetylcysteinate (TGA). Animals received a single dose of TGA (15 mg/kg, subcutaneously) immediately after intra-tracheal infection with Haemophilus influenzae (about 10⁷ CFU/animal). Serum and lung concentrations of TAP were determined at 0, 1, 3, 6, 12 and 24 h after drug administration by means of HPLC. TAP serum levels were elevated at 1 h and remained detectable for 24 h after drug administration. Tissue lung levels were comparable to peak serum concentrations but remained higher and decreased more slowly than serum concentrations.     

具明胶交联现象的氟伐他汀钠胶囊溶出度方法研究

目的 针对氟伐他汀钠胶囊交联现象建立溶出度试验方法,为修订现行氟伐他汀钠胶囊溶出度标准提供依据。方法 通过比较氟伐他汀钠胶囊国内外现行标准中溶出度方法,比对国内2家公司样品在4种pH条件下的溶出曲线相似度,考察样品在水和木瓜蛋白酶溶液（酶活力≥ 550 U·mL^-1）这2种溶出介质中的平均溶出度,确定溶出度检查方法：桨法,50 r·min^-1,溶出介质为500 mL水,30 min取样,HPLC测定,限度为标示量的80%;若出现不符合规定情况,以含木瓜蛋白酶溶液（酶活力≥ 550 U·mL^-1）为溶出介质,照上述方法重新试验,应符合规定。结果 本品未发生交联样品批次在水和木瓜蛋白酶溶液中的溶出结果一致,发生交联样品批次在加酶溶出介质中平均溶出量提高5%~7%。结论 该方法重现性好、准确、可靠,能客观反映本品的溶出情况,为统一和修订本品现行标准中溶出度项目提供了依据。     

In Vivo and In Vitro Diclofenac Sodium Evaluation After Rectal Application of Soft Gelatine Capsules Enabling Application Induced Transformation (AIT) into a Semisolid System of Liquid Crystals (SSLC) for Controlled Release

Purpose. Reverse micellar solutions of diclofenac sodium were encapsulated in soft gelatine capsules. On contact with aqueous media they exhibited an application induced transformation (AIT) into a semisolid system of liquid crystals (SSLC) which slows down drug release. The aim of the present paper was to study in vitro and in vivo drug release from these systems after rectal application. Methods. In vitro drug release was determined in a self-constructed dissolution apparatus to simulate rectal application. For in vivo bioavailability studies rabbits were used as animal models. In vitro release and in vivobioavailability of the capsules was compared to Voltaren^® suppositories. Results. The release profiles of the in vitro experiments show zero-order kinetics. The in vivo bioavailability studies show bioequivalence in terms of AUC for both formulations (capsules and Voltaren^® suppositories). The mean residence time (parameter of sustained release) of the capsules is three time longer in comparison to Voltaren^® suppositories. Conclusions. Rectal administration of capsules provides an appropiate route for controlled release via AIT-SSLC which could be clearly verified in rabbits.     

美洛昔康片剂与胶囊剂溶出度的比较

目的　测定 5个不同厂家的美洛昔康片剂与胶囊剂的溶出度 ,考察产品质量。方法　采用紫外分光光度法测定美洛昔康片剂与胶囊剂的溶出度。结果　 5个不同厂家的美洛昔康片剂及胶囊剂 45min内均溶出 70 %以上 ,溶出度参数T₅₀ 、T_d、T₈₀、m及溶出速率常数Kr均存在显著性差异 (P<0.01)。结论　不同厂家产品的内在质量存在差异 ,提示临床用药时应加以注意。     

电感耦合等离子体质谱法检测明胶空心胶囊中10种元素的含量

目的 建立用电感耦合等离子体质谱（ICP-MS）测定明胶空心胶囊中钒、铬、锰、镍、铜、砷、锶、镉、钡、铅10种元素含量的方法。方法 微波消解法处理明胶空心胶囊,用ICP-MS同时检测明胶空心胶囊中10种元素的含量。结果 10种元素的方法检出限范围为0.011~0.203ng·mL1,线性关系良好（r〉0.999）,回收率为85%~115%,RSD〈10%。结论 本方法准确可靠、灵敏便捷,可用于明胶空心胶囊中多种元素的测定。