HPLC测定非诺贝特缓释胶囊的有关物质

目的 建立非诺贝特缓释胶囊有关物质的HPLC测定方法。方法 采用Kromasil-100-5 C₁₈柱,流动相为乙腈-水（用磷酸调节pH至3.0）（67：33）;流速1.0 mL·min^-1;检测波长为286 nm;柱温为40℃;进样量为10 μL。结果 非诺贝特与其他杂质的分离度较好,非诺贝特的线性范围为0.54~3.23 μg·mL^-1（r=0.999 9）,检测限为0.03 μg·mL^-1。结论 建立的方法简便、准确、专属性强,可作为非诺贝特缓释胶囊有关物质的检测方法。     

HPLC梯度洗脱法测定葡萄糖酸依诺沙星注射液的有关物质

摘 要 目的： 建立梯度洗脱的HPLC法测定葡萄糖酸依诺沙星注射液中有关物质。方法: 色谱柱：Diamonsil^TM C₁₈(250 mm×4.6 mm,5 μm);流动相A：0.025 mol·L^-1磷酸溶液（三乙胺调pH3.0）甲醇-乙腈（80∶10∶10）,流动相B：0.025 mol·L^-1磷酸溶液（三乙胺调节pH3.0）-甲醇-乙腈（350∶325∶325）,梯度洗脱;流速：1.1 ml·min^-1;检测波长：269 nm、284 nm;进样量：20 μl;柱温：40℃。结果:在该色谱条件下,供试品稳定性及分离度良好。5-羟甲基糠醛在19.80 ng·ml^-1～19.80 μg·ml^-1范围内与峰面积呈良好的线性关系(r=0.999 9),检出限为0.18 ng,平均回收率为99.68%,RSD为0.12%(n=9)。结论: 本法结果准确、灵敏度高、专属性强、重复性好,可用于葡萄糖酸依诺沙星注射液有关物质的检测。     

HPLC法测定复方维生素B6凝胶剂中维生素B6与醋酸氟轻松的含量

摘 要 目的：建立复方维生素B₆凝胶剂中维生素B₆与醋酸氟轻松的含量测定方法。方法: 采用HPLC法,色谱柱：Lichrospher CNC₁₈柱（250 mm×4.6 mm, 5 μm）;流动相：庚烷磺酸钠溶液（称取6.8 g磷酸二氢钾和1.0 g庚烷磺酸钠,加水溶解并稀释至1 000 ml）-甲醇-三乙胺（35∶65∶0.2）,用磷酸调pH至3.2;检测波长：238 nm;柱温：25℃;进样量：20 μl。结果: 维生素B₆在15.0～300.0 μg·mL^-1浓度范围内线性关系良好（r=1.0000）,平均回收率为99.65%,RSD为0.3%（n=9）;醋酸氟轻松在0.4～8.0 μg·mL^-1浓度范围内线性关系良好（r=0.999 0）,平均回收率为99.35%,RSD为0.85%（n=9）。结论:该方法简便,重复性好,测定的结果准确,可用于复方维生素B₆凝胶剂的含量测定。     

HPLC法测定注射用卡非佐米的含量

摘 要 目的：建立高效液相色谱法测定注射用卡非佐米含量的方法。方法: 使用Waters symmetry C₁₈（250 mm×4.6 mm, 5 μm）色谱柱,样品溶剂为甲醇,流动相为0.05%三氟乙酸水-乙腈（57∶43）,流速为1.0 ml·min^-1,波长210 nm,柱温25℃,进样体积10 μl。结果: 结果卡非佐米线性范围为120～600 μg·mL^-1(r=0.999 7),平均回收率为100.4%,RSD为0.24%（n=9）。结论:本方法能够快速有效地测定注射用卡非佐米的含量。     

HPLC法同时测定大败毒胶囊中绿原酸、咖啡酸和阿魏酸的含量

摘 要 目的: 建立HPLC法同时检测大败毒胶囊中绿原酸、咖啡酸和阿魏酸的测定方法。方法: 采用Agilent C₁₈（250 mm×4.6 mm,5 μm）色谱柱;乙腈-0.4%磷酸溶液（15∶85）为流动相,流速：1.0 ml·min^-1;检测波长：324 nm。柱温:30℃,进样量：10 μl。结果:线性范围：绿原酸5.42～32.43 μg·ml^-1(r=0.999 8),咖啡酸2.63～26.32 μg·ml^-1(r=0.999 4),阿魏酸1.44～14.44 μg·ml^-1(r=0.999 9);平均回收率：绿原酸99.98%,RSD=0.2%(n=6),咖啡酸99.31%,RSD=0.4%(n=6),阿魏酸99.48%,RSD=0.8%(n=6)。结论:该方法操作简便、准确,重复性好,可用于测定大败毒胶囊中绿原酸、咖啡酸和阿魏酸的含量。     

HPLC法测定醋甲唑胺片的含量和有关物质

摘 要 目的： 建立高效液相色谱法测定醋甲唑胺片的含量和有关物质。方法: 色谱柱为Symmetry C₁₈（150 mm×4.6 mm,5 μm）;流动相为乙腈-0.1 mol·L^-1醋酸钠（pH4.5）（20∶80）;流速:1.0 ml·min^-1;检测波长:252 nm;柱温:30℃;进样量:20 μl。结果: 醋甲唑胺浓度在10.0～80.0 μg·mL^-1范围内峰面积值呈良好的线性关系（r=0.999 7）,平均加样回收率为99.56%,RSD=0.95%(n=9)。测得3批样品杂质含量分别为0.25%,0.21%,0.23%。结论: 本法简便、准确,专属性好,精密度高,专属性好,可用于醋甲唑胺片的含量和有关物质测定。     

HPLC法同时测定复方阿托伐他汀钙苯磺酸氨氯地平片中两种药物的含量

摘 要 目的： 建立测定复方阿托伐他汀钙苯磺酸氨氯地平片中两种药物含量的RP-HPLC法。方法: 采用 Gemini-NX C₁₈色谱柱（250 mm×4.6 mm,5 μm）,以20 mmol·L^-1磷酸二氢钾溶液（用磷酸调至pH至4.0）-乙腈-甲醇（30∶10∶60）为流动相,流速为1.0 ml·min^-1,检测波长为240 nm,柱温为30℃,进样量为20 μl。结果: 阿托伐他汀和氨氯地平浓度分别在0.4~40.0 μg·mL^-1和0.2~20.0 μg·mL^-1范围内线性关系良好,两者的平均回收率分别为100.6%和99.7%,RSD分别为0.92%和0.85%（n=9）。结论:该法专属性强、稳定可靠,可用于复方阿托伐他汀钙苯磺酸氨氯地平片中两种药物的含量测定。     

HPLC梯度洗脱法测定氯替泼诺妥布霉素复方混悬滴眼液中氯替泼诺含量及有关物质

摘 要 目的： 建立HPLC梯度法测定氯替泼诺妥布霉素复方混悬滴眼液中氯替泼诺含量及有关物质。方法: 采用HPLC法,色谱柱：Inertsil ph苯基柱（250 mm×4.6 mm,5 μm）;流动相A：0.25%醋酸溶液 乙腈（80∶20）;流动相B：乙腈;流速：2.0 ml·min^-1,进行线性梯度洗脱;检测波长：244 nm;柱温：30℃;进样量：20 μl。结果: 主成分与各杂质峰分离度良好。氯替泼诺浓度在0.001~1.02 mg·mL^-1（r=0.999 9）范围内与峰面积线性关系良好,平均回收率为99.9%,RSD为0.9%（n=9）。结论:该方法灵敏准确,色谱峰分离完全,可用于氯替泼诺妥布霉素混悬滴眼液的质量控制。     

HPLC法同时测定野豌豆中芦丁、金丝桃苷和槲皮素的含量

〗摘 要 目的： 建立野豌豆药材中芦丁、金丝桃苷和槲皮素三个活性成分的HPLC含量测定方法。 方法: 采用Agilent ZORBAX Eclipse XDB C₁₈色谱柱(250 mm×4.6 mm,5 μm),流动相为乙腈 1‰磷酸水溶液,梯度洗脱,流速:0.8 ml·min^-1,检测波长:370 nm,柱温：30℃。结果:芦丁、金丝桃苷和槲皮素的线性范围分别为4.090～130.940 μg ·ml^-1(r=0.999 9)、4.600～147.200 μg ·ml^-1(r=0.999 9)和0.810～25.780 μg·ml^-1(r=0.999 8);平均回收率分别为103.45%（RSD=1.25%）、98.96%（RSD=1.77%）和102.88%（RSD=0.84%）（n=6）。结论: 本方法稳定,重复性好,操作简单,可用于野豌豆药材的质量控制。     

HPLC法同时测定蒲药灌肠液中3个有效成分的含量

摘 要 目的： 建立蒲药灌肠液中香蒲新苷、异鼠李素-3-O-新橙皮苷和延胡索乙素的HPLC含量测定方法。方法: 采用ZORBAX SB-C₁₈色谱柱（250 mm×4.6 mm,5 μm）,以乙腈-0.1%磷酸（三乙胺调节pH至6.0）为流动相,梯度洗脱程序,流速:1.0 ml·min^-1,检测波长为254 nm（0～14 min）和281 nm（14～25 min）,柱温:30 ℃。结果: 香蒲新苷、异鼠李素-3-O-新橙皮苷和延胡索乙素的线性范围分别为19.840～198.400 μg·ml^-1（r=0.999 6）、20.520～205.200 μg·ml^-1（r=0.999 8）和10.040～100.400 μg·ml^-1（r=0.999 7）,回收率分别为98.8%、98.6%和98.9%,RSD分别为1.4%、1.6%和1.3%（n=6）。结论: 该方法灵敏度高,专属性强,可用于蒲药灌肠液的质量控制。     

Fenofibrate

Fenofibrate is a fibric acid derivative with lipid-modifying effects that are mediated by the activation of peroxisome proliferator-activated receptor-α. Fenofibrate also has a number of nonlipid, pleiotropic effects (e.g. reducing levels of fibrinogen, C-reactive protein, and various pro-inflammatory markers, and improving flow-mediated dilatation) that may contribute to its clinical efficacy, particularly in terms of improving microvascular outcomes. The beneficial effects of fenofibrate on the lipid profile have been shown in a number of randomized controlled trials. In primary dyslipidemia, fenofibrate monotherapy consistently decreased triglyceride (TG) levels to a significantly greater extent than placebo; significantly greater increases in high-density lipoprotein cholesterol (HDL-C) levels and significantly greater reductions in low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels were also seen in some trials. Monotherapy with fenofibrate or gemfibrozil had generally similar effects on TG and HDL-C levels, although in one trial, TC and LDL-C levels were reduced to a significantly greater extent with fenofibrate than with gemfibrozil. Fenofibrate monotherapy tended to improve TG and HDL-C levels to a significantly greater extent than statin monotherapy in primary dyslipidemia, whereas statin monotherapy decreased LDL-C and TC levels to a significantly greater extent than fenofibrate monotherapy. Fenofibrate also had a beneficial effect on atherogenic dyslipidemia in patients with the metabolic syndrome or type 2 diabetes mellitus, reducing TG levels, tending to increase HDL-C levels, and promoting a shift to larger low-density lipoprotein particles. In terms of cardiovascular outcomes, fenofibrate did not reduce the risk of coronary heart disease (CHD) events to a greater extent than placebo in patients with type 2 diabetes in the FIELD trial. However, the risk of some nonfatal macrovascular events (e.g. nonfatal myocardial infarction, revascularization) and certain microvascular outcomes (e.g. amputation, first laser therapy for diabetic retinopathy, progression of albuminuria) was reduced to a significantly greater extent with fenofibrate than with placebo. Subgroup analysis revealed a significant reduction in the cardiovascular disease (CVD) event rate among fenofibrate recipients in the subgroup of patients with marked hypertriglyceridemia or marked dyslipidemia at baseline. In the ACCORD Lipid trial, there were no significant differences between patients with type 2 diabetes and a high risk of CVD events who received fenofibrate plus simvastatin and those who received placebo plus simvastatin for any of the primary or secondary cardiovascular outcomes. However, fenofibrate plus simvastatin was of benefit in patients who had markedly high TG levels and markedly low HDL-C levels at baseline. In addition, fenofibrate plus simvastatin slowed the progression of diabetic retinopathy. Fenofibrate is generally well tolerated. Common adverse events included increases in transaminase levels that were usually transient, minor, and asymptomatic, and gastrointestinal signs and symptoms. In conclusion, monotherapy with fenofibrate remains a useful option in patients with dyslipidemia, particularly in atherogenic dyslipidemia characterized by high TG and low HDL-C levels.     

国产非诺贝特片与进口非诺贝特胶囊人体生物等效性研究

目的:评价国产非诺贝特片与进口非诺贝特胶囊人体生物等效性。方法:采用双周期双交叉试验设计,将24名健康受试者随机平均分为2组,在每个给药周期,单次口服受试制剂或参比制剂非诺贝特200 mg,以高效液相色谱法测定血浆中非诺贝酸的浓度,药-时数据经DAS2.1统计软件处理,计算主要药动学参数,并评价二者的生物等效性。结果:非诺贝特片和非诺贝特胶囊的主要药动学参数分别为:t_1/2（18.5±4.3）、（19.3±4.4）h,C_max（9.0±3.3）、（8.7±2.8）μg·ml^-1、t_max（5.3±0.9）、（5.0±0.8）h、AUC_0-72h（128.1±37.7）、（134.2±42.1）μg·h·ml^-1,AUC_0-∞（140.1±41.6）、（146.8±97.4）μg·h·ml^-1。非诺贝特片的相对生物利用度F_0-72h为（91.6±3.4）%,F_0-∞为（92.6±2.5）%,受试制剂AUC_0-72h和C_max的90%可信限分别落在参比制剂的90.4%～102.0%和87.2%～116.8%范围内。结论:2种制剂具有生物等效性。     

国家食品药品监督管理局国家药品标准修订——非诺贝特分散片

本品含非诺贝特(C₂₀H₂₁ClO₄)应为标示量的93.0%~107.0%。     

Micronized Fenofibrate in Dyslipidemia

▲ The prodrug fenofibrate, a synthetic phenoxy-isobutyric acid derivative, is rapidly hydrolyzed in vivo to form fenofibric acid, which alters plasma lipid levels by activating the peroxisome proliferator-activated receptor α. ▲ The micronized fenofibrate 200mg capsule formulation, and the recently developed micronized fenofibrate 160mg tablet formulation, are bioequivalent. ▲ Micronized fenofibrate 200 mg/day (capsules) increased high density lipoprotein cholesterol (HDL-C) levels significantly from baseline in up to 7098 patients with various dyslipidemias in noncomparative studies. ▲ Micronized fenofibrate 200 mg/day (capsules) produced significantly greater elevations in HDL-C levels than a variety of HMG-CoA reductase inhibitors in small, randomized, double-blind and nonblind studies in patients with dyslipidemia (n = 91 to 227). This formulation of fenofibrate and gemfibrozil produced similar increases in HDL-C levels in a randomized, double-blind study (n = 234). ▲ Micronized fenofibrate 160mg once daily (tablet) increased HDL-C levels significantly from baseline by 10.6 to 14.5% in patients with type IIa or IIb dyslipidemia (n = 353) in two noncomparative studies. Additionally, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and LDL-C to HDL-C and TC to HDL-C ratios were lowered significantly from baseline. ▲ The tablet and capsule formulations of fenofibrate were both generally well tolerated in two noncomparative studies in 375 or 9884 patients. In double-blind, placebo-controlled trials in a total of 804 patients, the pooled incidences of individual adverse events were generally similar with fenofibrate and placebo.     

Fenofibrate and human liver

In rodents fenofibrate shares with other triglyceride-lowering agents the potential to increase the liver peroxisome population. It was therefore of interest to look for this effect in hyperlipoproteinemic patients receiving this drug. Light and electron microscopy of liver biopsies from a group of 10 patients treated with fenofibrate and from another group of 15 receiving diet only, show no morphological difference between both groups. In contrast with the rodent data the morphometric study reveals no significant changes in the number (fenofibrate group: 7.96 10(10) cm-3; group receiving diet alone: 8.41 10(10) peroxisomes/cm3 of liver tissue) or in the size (fenofibrate group: Diameter = 0.53 +/- 0.07 micrometer--group receiving diet alone: 0.50 +/- 0.06) of peroxisomes. The difference between our results and those obtained consistently in rodents may be due to the relatively low dose in man and/or a species-dependent difference in enzyme content of liver peroxisomes, itself related to an apparent difference in the way in which lipids are handled.     

HPLC测定清洁验证残留物非诺贝特的含量

目的：建立清洁验证中残留物非诺贝特含量测定的高效液相色谱法。方法：色谱柱为 Agilent ZORBAX SB-C18（150 mm×4.6 mm,5μm）,流动相为水（磷酸调节pH至2.5）-乙腈（30∶70）,检测波长：286 nm,流速：1.0 mL/min,柱温：25℃,进样量：20μL。结果：非诺贝特在0.09～0.90μg/mL范围内线性关系良好, r2=0.9994;回收率：99.69%,RSD =0.16%（n=9）。结论：该法操作简便、结果准确,可以用于清洁验证残留物非诺贝特的定量分析。     

非诺贝特制剂的研究进展

非诺贝特属于贝特类降血酯药,是降低甘油三酯的首选药物之一,临床使用率高。由于非诺贝特难溶于水,不易于被吸收,导致生物利用度较低,影响药物疗效。为解决这一问题,不同类型的药物传递系统被应用与研究。本文综述非诺贝特制剂的研究进展,以期为其制剂的进一步开发提供思路。     

Fenofibrate and warfarin interaction.

A 79-year-old man with atrial fibrillation and coronary heart disease who was taking warfarin (Coumadin) was converted to fenofibrate from gemfibrozil therapy for persistently elevated triglyceride levels. The patient took fenofibrate for 1 month and subsequently experienced rectal bleeding that required a visit to the emergency room. Before starting fenofibrate therapy, his coagulation values were within therapeutic range, but when measured in the emergency room the international normalized ratio (INR) was grossly elevated. The patient denied any changes in diet, alcohol ingestion, compliance with therapy, or use of other new drugs except for fenofibrate. His drug therapy profile consisted of digoxin, fosinopril, and furosemide for chronic heart failure, allopurinol for gout, and potassium supplementation. To minimize the risk of supratherapeutic INR values and/or hemorrhagic events, clinicians should perform serial monitoring of INR when initiating fenofibrate therapy in a patient previously stabilized on a coumarin anticoagulant.     

Fenofibrate: altered renal function

In patients with type 2 diabetes, a subgroup analysis of a placebo-controlled trial of fenofibrate showed a significant decline in calculated creatinine clearance with fenofibrate. Most fibrates seem to have a detrimental effect on renal function, with the probable exception of gemfibrozil, which is the fibrate of choice in the few situations in which a fibrate is needed.