富马酸替诺福韦双特戊酯有关物质的鉴定

目的:采用色谱-质谱联用技术对富马酸替诺福韦双特戊酯中有关物质进行结构鉴定。方法:采用BDS Hypersil C18(250 mm×4.6 mm,5μm)色谱柱,流动相为乙腈-0.2%醋酸铵溶液,梯度洗脱,对富马酸替诺福韦双特戊酯有关物质进行分离;LC-PDA测定各有关物质的UV吸收,甲醇辅助电喷雾正离子化LC-TOF和LC-MS/MS分别测定各有关物质的精密质量和二级质谱。结果:检测到富马酸替诺福韦双特戊酯中存在多个有关物质,其中仅3个的含量在0.1%以上,并鉴定出4个主要有关物质的结构。结论:色谱-质谱联用技术能够有效地鉴定药物中的有关物质,富马酸替诺福韦双特戊酯有关物质鉴定结果对其质量控制和工艺优化提供了参考依据。     

HPLC测定奥美沙坦酯氢氯噻嗪片含量和有关物质

目的:建立高效液相色谱法(HPLC)测定奥美沙坦酯氢氯噻嗪片含量和有关物质的测定方法。方法:采用HPLC,色谱柱:C1(84.6mm×250mm,Kromasil);流动相A:0.02mol/L磷酸二氢钠溶液(用磷酸调节pH至3.0),流动相B:甲醇-乙腈(100∶900),梯度洗脱。结果:奥美沙坦酯和氢氯噻嗪均能与其他杂质较好分离;奥美沙坦酯浓度在0.002026~0.04052mg/mL(r=0.999)范围内线性良好,氢氯噻嗪在0.001265~0.02530mg/mL范围内线性良好(r=1.000)。结论:本方法灵敏、准确,可作为奥美沙坦酯氢氯噻嗪片含量和有关物质的测定方法。     

奥美沙坦酯中有关物质的HPLC测定

建立了高效液相色谱法测定奥美沙坦酯中的有关物质.采用C18色谱柱,以30mmol/L磷酸二氢钾溶液(用磷酸调至pH 3.5)-甲醇(40:60)为流动相,检测波长256nm.在此条件下奥美沙坦酯与其合成中间体、降解产物分离情况较好.     

奥美沙坦酯及其相关物质的分离与测定

目的：建立反相高效液相色谱法分离测定奥美沙坦酯及其相关物质。方法：HPLC色谱条件：色谱柱为Inertsil ODS-2（4．6mm×250mm，5μm），柱温为25℃；以乙腈-磷酸盐缓冲液为流动相，进行梯度洗脱；流速为1．0mL·min^-1；检测波长为240nm。结果：明确了奥美沙坦酯合成中可能引入的杂质A，B，C，D，E以及奥美沙坦酯的出峰位置；杂质A，B，C，D，E的校正因子（相对于奥美沙坦酯）分别为0．90，0．88，1．07，1．04，1．13；在奥美沙坦酯原料中共检测到6个杂质，其中杂质A和杂质D含量均大于0．1％。结论：采用加校正因子的1％主成分自身对照法和杂质外标对照法均能直接反映奥美沙坦酯中相关物质情况。     

地佐辛注射液有关物质的色谱-质谱结构鉴定

目的：采用色谱-质谱联用技术鉴定地佐辛注射液中的有关物质。方法：采用Agilent Eclipse Plus C₁₈(150 mm×4.6 mm,5μm)色谱柱,以甲醇-10 mmol·L^-1甲酸铵缓冲溶液(甲酸调节pH至2.7)为流动相梯度洗脱,对地佐辛注射液有关物质进行分离,电喷雾正离子化-四极杆-飞行时间串联高分辨质谱(ESI-Q-TOF/MS)测定各有关物质母离子及其子离子的准确质量和元素组成,通过光谱解析鉴定其结构。结果：在所建立的分析条件下,地佐辛及其有关物质分离良好,检测并鉴定出地佐辛注射液及其强制降解试验样品中20个含量大于0.1%的有关物质,其中2个为已知杂质,其他杂质均未见报道。结论：色谱-质谱联用技术能有效地分离鉴定地佐辛注射液中的有关物质,为其质量控制提供参考依据。     

坎地沙坦酯氨氯地平片中降解产物的研究简

目的确定坎地沙坦酯氨氯地平片中降解产物的来源。方法采用2种不同色谱条件的高效液相色谱法（HPLC）和液相色谱-质谱／质谱（LC—MS／MS）分析方法确定坎地沙坦酯氨氯地平片中降解产物与坎地沙坦酯片中有关物质的关系。结果3种方法的结果显示,坎地沙坦酯氨氯地平片中的降解产物和坎地沙坦酯片中的有关物质一致。结论坎地沙坦酯氨氯地平片中的5个降解产物分别与坎地沙坦酯有关物质Ⅱ,Ⅲ,Ⅳ,Ⅴ,Ⅵ相对应。     

应用LC-ESI-FTICRMS/MS~n技术研究吗替麦考酚酯原料药中有关物质

目的:分离鉴定吗替麦考酚酯(MMF)原料药中的有关物质。方法:采用液相色谱-电喷雾-傅立叶变换离子回旋共振质谱(LC-ESI-FTICRMS/MSn)技术对MMF原料药进行分析,获得主成分及有关物质的高分辨质谱数据(HRMS)和多级质谱数据(MSn),并对有关物质结构进行推断。结果:结合文献数据和质谱裂解规律,从MMF原料药中初步鉴定出6种有关物质。结论:在初步鉴定出的6种有关物质中,有3种与欧洲药典和美国药典收载的杂质相同,还有3种不同,说明同一原料药在不同生产工艺和环境条件下所产生的有关物质不尽相同,因此亟需建立符合我国实际情况的药品质量安全标准。     

间苯三酚注射液有关物质的二维液相色谱-质谱联用鉴定

采用二维液相色谱-质谱联用技术鉴定间苯三酚注射液中的有关物质。以HSS T3 (250 mm×4.6 mm5μm)为色谱柱,1.36 g·L^-1磷酸二氢钾(稀磷酸调节pH调至3.0)-乙腈为一维流动相进行梯度洗脱,实现间苯三酚注射液有关物质的分离。各分离成分经多通道切换阀分别被捕集于截留管中,然后输送到BDS C18 (100 mm×4.6 mm2.4μm)色谱柱,以0.1%甲酸水溶液-甲醇为二维流动相,进行梯度洗脱实现快速脱盐。电喷雾负离子化-四极杆-飞行时间串联高分辨质谱检测各有关物质母离子及其子离子的准确质量和元素组成,通过质谱解析、有机反应机制分析,甚至对照品对照鉴定它们的结构。在所建立的分析条件下,间苯三酚及其有关物质分离良好,首次检测并鉴定出间苯三酚注射液及其强制降解实验样品中17个主要有关物质,鉴定结果可为间苯三酚注射液质量控制提供参考依据。     

抗高血压药奥美沙坦酯合成新路线和相关杂质的研究

目的研究奥美沙坦酯的新合成方法，并对合成中产生的主要杂质进行结构确证和有效控制。方法4-(1-羟基-1-甲基乙基)-2-丙基咪唑-5-羧酸乙酯水解，环合成4,4-二甲基-2-丙基-4,6-二氢呋喃并［3,4-d］咪唑-6-酮，与4-［2-(2-三苯甲基四唑-5-基)苯基］苄基溴缩合，经分离纯化，皂化成钠盐，与4-氯甲基-5-甲基-2-氧代-1,3-二氧杂环戊烯成酯，脱保护基得奥美沙坦酯。对缩合反应的主要杂质应用X-ray单晶衍射谱确证其结构为咪唑位置异构体，并用其合成奥美沙坦酯的咪唑位置异构体。通过优化反应条件抑制异构体的量，从而保证奥美沙坦酯的质量。结果用新路线合成了奥美沙坦酯，总收率60%，纯度大于99.0%；成品中异构体含量小于0.1%。结论本文合成路线是奥美沙坦酯的新合成方法，并首次报道奥美沙坦酯的咪唑位置异构体。     

基于UPLC-Q-TOF-MS/MS技术分析利拉萘酯中主要杂质

目的采用液相色谱-四极杆飞行时间串联质谱法(HPLC-Q-TOF-MS)分析利拉萘酯原料中主要杂质并对其结构进行鉴定。方法色谱柱为Agilent Extend C18(2.1×100 mm,1.8μm),流动相为0.1%甲酸水(A)-乙腈(B),梯度洗脱,体积流量为0.4m L/min;离子源:ESI离子源;扫描模式:正离子扫描。结果根据各降解杂质的二级质谱图以及高分辨数据,利拉萘酯原料中主要存在6个有关物质,主要来源于原料中间体和降解产物。结论建立的方法能有效地分离主成分利拉萘酯与有关物质,为利拉萘酯原料药的质量控制、工艺优化及贮存提供参考。     

Identification of a degradation product in stressed tablets of olmesartan medoxomil by the complementary use of HPLC hyphenated techniques

An unknown degradation product (DP-1) increased in olmesartan medoxomil (OLM) tablets stored at 40 degrees C/75% r.h., reaching 0.72% after 6 months. The molecular weight and fragment information obtained by LC-MS suggested that DP-1 was a dehydrated dimer of olmesartan (OL) and the presence of ester carbonyl group was indicated by solvent-elimination LC-IR analysis. LC-(1)H NMR confirmed the structure of DP-1 as an esterified dimer of OL. Rapid and accurate identification of the degradation product was achieved by the complementary use of HPLC hyphenated techniques without complicated isolation or purification processes.     

LC-MS/MS法分析注射用头孢西丁钠中的有关物质

目的:建立LC-MS/MS法分析注射用头孢西丁钠中的有关物质。方法:采用Thermo Syncronis C18(4.6 mm×250 mm,5μm)色谱柱,以1%甲酸水溶液(A)-乙腈(B)为流动相,1.0 mL.min-1线性梯度洗脱分离;柱后分流,电喷雾离子化MS测定。采集有关物质的PDA谱、质谱母离子及子离子谱,并进行解析,推测有关物质的结构。结果:在所建立的条件下,头孢西丁钠及其有关物质分离良好,检测出15个有关物质,并对其进行结构解析。结论:建立的LC-MS/MS法能有效地分离分析头孢西丁钠及其有关物质,为注射用头孢西丁钠的质量控制和工艺优化提供了参考。     

奥美沙坦氢氯噻嗪片在中国健康志愿者体中的药代动力学

目的:研究单次、多次口服奥美沙坦氢氯噻嗪片在中国健康受试者体内的药代动力学。方法:本研究为随机、开放、单次和多次口服给药的单中心试验。12位健康受试者单次和多次口服1片奥美沙坦氢氯噻嗪片(每片含奥美沙坦20 mg,氢氯噻嗪12.5 mg),采用HPLC-MS-MS法测定奥美沙坦和氢氯噻嗪的血浆药物浓度,利用DAS2.0和SPSS 13.0计算药动学参数和进行统计学分析。结果:单次和多次口服给药后奥美沙坦的药动学参数如下:Cmax分别为(489±122)μg/L和(531±125)μg/L,AUC0→t分别为(3468±869)μg.L-1.h和(3557±1209)μg.L-1.h,tmax分别为(2.6±0.5)h和(2.3±0.8)h,t1/2分别为(7.3±4.0)h和(8.3±3.6)h;单次和多次口服给药后氢氯噻嗪的药动学参数如下:Cmax分别为(122±34)μg/L和(182±39)μg/L,AUC0→t分别为(764±211)μg.L-1.h和(1079±361)μg.L-1.h,Cmax分别为(2.2±0.7)h和(1.6±0.6)h,t1/2分别为(6.8±2.3)h和(7.1±1.6)h。结论:奥美沙坦氢氯噻嗪片主要药动学参数单剂量和多剂量给药差异无统计学意义,奥美沙坦和氢氯噻嗪在人体内均无明显蓄积。     

Use of 24-Hour Ambulatory Blood Pressure Monitoring to Assess Antihypertensive Efficacy

INTRODUCTION: Goal rates, the percentage of patients with hypertension achieving recommended SBP/DBP, are a clinically important assessment of an antihypertensive agent's efficacy. Twenty-four-hour ambulatory blood pressure monitoring (ABPM) allows accurate assessment of a patient's hypertension and risk for cardiovascular events, and provides the most accurate measure of an antihypertensive agent's efficacy throughout a 24-hour dosing interval. METHODS: A 12-week (4-week single-blind placebo run-in phase followed by an 8-week double-blind active treatment phase) randomized, parallel-group study reported that the recommended starting dose of the angiotensin II receptor antagonist (angiotensin receptor blocker; ARB) olmesartan medoxomil (Benicar(trade mark)) 20 mg/day was more effective than starting doses of losartan potassium (Cozaar) 50 mg/day, valsartan (Diovan) 80 mg/day, or irbesartan (Avapro) 150 mg/day in reducing cuff DBP in patients with essential hypertension. The present report includes analyses of secondary efficacy variables from this 12-week trial. RESULTS: The mean reduction in blood pressure from baseline to week 8 (end of treatment) was significantly greater with olmesartan medoxomil than with valsartan for all ABPM times analyzed (24 hours, daytime, night-time, and last 2 and 4 hours of monitoring). Statistical significance was reached for comparisons of olmesartan medoxomil with losartan potassium for a majority of times analyzed and with irbesartan for SBP in the last 4 hours of monitoring. Goal rates for accepted critical ambulatory blood pressure (ABP) values of <130/80 mm Hg for mean 24-hour ABP, <135/85 mm Hg for mean daytime ABP, and <120/75 mm Hg for mean night-time ABP were significantly greater for patients receiving olmesartan medoxomil than for those receiving losartan potassium or valsartan. Goal rates were numerically superior, but not statistically significant, to those achieved with irbesartan. Compared with losartan potassium or valsartan recipients, a significantly higher percentage of patients treated with olmesartan medoxomil achieved the 24-hour ABP goal of <130/85 mm Hg. The last 2 and 4 hours of ABPM indicated that olmesartan medoxomil maintained larger mean decreases in blood pressure through the morning surge. DISCUSSION/CONCLUSION: ABP goal rates are a meaningful measure of antihypertensive efficacy. The effects on mean change from baseline in ABP and ABP goal rates after 8 weeks of treatment were numerically better, but not statistically significant, for olmesartan medoxomil than for irbesartan. However, olmesartan medoxomil was significantly more effective than losartan potassium or valsartan.     

Efficacy and Safety of Olmesartan Medoxomil and Hydrochlorothiazide Compared with Benazepril and Amlodipine Besylate

BACKGROUND: Most patients with stage 2 hypertension require two or more antihypertensive agents in order to achieve the BP goals recommended in current treatment guidelines. Accordingly, combinations of two drugs with different mechanisms of antihypertensive action are widely used. OBJECTIVE: The aim of this randomized, double-blind, multicenter 12-week study was to compare the efficacy, safety, and tolerability of a combination of olmesartan medoxomil/hydrochlorothiazide (HCTZ) with that of benazepril plus amlodipine besylate in patients with stage 2 hypertension. METHODS: Patients were eligible for randomization following a 3- to 4-week placebo run-in period if they had either (i) mean seated DBP>or=90 mm Hg but<115 mm Hg and mean seated SBP>or=160 mm Hg but <200 mm Hg, or (ii) mean seated DBP>or=100 mm Hg but<115 mm Hg. The difference in mean seated SBP measured on two separate visits during the run-in period was required to beor=95 mm Hg and<115 mm Hg or SBP>145 mm Hg and相似文献   

替加氟有关物质的色谱-质谱结构鉴定

目的采用色谱-质谱联用技术鉴定替加氟有关物质,为其工艺和质量控制提供参考依据。方法采用十八烷基硅烷键合硅胶的填充剂,流动相为乙腈-甲醇-10 mmol·L-1醋酸铵缓冲溶液,对替加氟有关物质进行分离;采用电喷雾正离子化-飞行时间质谱法测定各有关物质的准确质量,三重四极杆质谱测定子离子特征,并经解析鉴定各杂质结构。结果与结论替加氟与其有关物质分离良好,检测出4个主要有关物质均为替加氟合成的起始原料,是母核基本未发生变化,仅5位被不同基团取代的衍生物。     

LC-MS/MS法鉴定注射用多西他赛中的有关物质

采用LC-MS/MS法对注射用多西他赛中的有关物质进行鉴定。采用乙酸乙酯提取注射剂,以去除制剂中影响LC-MS/MS离子化效果的磺丁基-β-环糊精等辅料,然后对提取物中的有关物质进行LC-MS/MS鉴定。采用LC-ESI-MS/MS测定各有关物质的一级和二级质谱图,并对准分子离子的各个产物离子进行归属,对各杂质可能的结构进行推测。在所建立的条件下,多西他赛及其有关物质分离良好,共鉴定了注射用多西他赛中的9个有关物质结构,其中4个有关物质为首次在注射用多西他赛中发现。本文所建立的LC-MS/MS法可以有效地分离分析多西他赛及其有关物质,为其制剂的质量控制和工艺优化提供参考。