HPLC法测定盐酸丙酰左卡尼汀原料药及其制剂的含量和有关物质

目的:建立测定盐酸丙酰左卡尼汀原料药及其制剂含量和有关物质的方法。方法:采用高效液相色谱法测定3批盐酸丙酰左卡尼汀原料药及注射用制剂中主成分及杂质A、B、C的含量。色谱柱为Angilent Eclipse XDB-C18,流动相为0·006mol·L-1辛烷磺酸钠溶液(pH3·0)-甲醇(95:5),流速为1·0mL·min-1,柱温为30℃,检测波长为210nm。结果:盐酸丙酰左卡尼汀色谱峰与杂质峰能完全分离,主成分检测浓度线性范围为1·0036～20·072mg·mL-1(r=0·9997);低、中、高浓度平均回收率分别为99·92%、100·62%、100·25%,RSD为1·68%、2·41%、2·12%(n=9);最低检测限为0·03888mg·mL-1;6批样品中总杂质含量均小于1·930%。结论:本法简单、灵敏、专属性强、结果准确,适用于测定盐酸丙酰左卡尼汀原料药及其制剂的含量和有关物质。     

盐酸丙酰左卡尼汀片在健康人体中的药代动力学研究

目的考察盐酸丙酰左卡尼汀片在健康志愿受试者单次和多次口服给药的药代动力学及进食对其的影响。方法单次给药时受试者分4组(0.5、1、2 g、安慰剂)平行进行,多次给药1组(1 g),进食影响2组(餐前给药、餐后给药)交叉进行。采用LC-MS/MS法检测丙酰左卡尼汀、乙酰左卡尼汀、左卡尼汀的浓度,采用DAS2.1.1药代动力学程序估算丙酰左卡尼汀、乙酰左卡尼汀、左卡尼汀药代动力学参数。结果单次给药3个剂量组(0.5、1、2 g)的主要药动学参数为:丙酰左卡尼汀Cmax:(428.84±165.49)、(489.67±231.73)、(2 202.99±1 373.44)μg.L-1;AUC(0-t):(6 208.91±2 138.44)、(7 248.55±2 557.87)、(14 266.30±7 386.05)μg.L-1.h-1。空腹和进食后单次给药后丙酰左卡尼汀的Cmax分别为(904.23±868.38)μg.L-1和(326.95±130.97)μg.L-1;AUC(0-t)分别为(8 678.42±2 864.59)μg.L-1.h-1和(4 009.97±1 736.10)μg.L-1.h-1。多次给药后丙酰左卡尼汀的MRT为(15.03±1.28)h;Cmaxss为(778.78±342.05)μg.L-1;Cminss为(245.75±164.40)μg.L-1;AUC(0-t)及AUCbc分别为(7 664.89±1 555.36)μg.L-1.h-1和(4 343.95±2 388.05)μg.L-1.h-1,Css为(638.74±129.61)μg.L-1,DF为(84.57±51.25)%。结论单次和多次口服盐酸丙酰左卡尼汀片后盐酸丙酰左卡尼汀的药代动力学过程基本相似;在0.5～2 g剂量范围内,盐酸丙酰左卡尼汀符合线性动力学特征,多次给药后盐酸丙酰左卡尼汀代谢物在体内无蓄积现象,进食对盐酸丙酰左卡尼汀的药代动力学参数有显著影响。     

盐酸丙酰左卡尼汀注射剂中有关物质及含量的测定

目的建立高效液相色谱法测定盐酸丙酰左卡尼汀有关物质和含量。方法色谱柱为Angilent Zorbax SB-C18柱(250 mm×4.6 mm,5μm);流动相为0.006 mol/L辛烷磺酸钠溶液(每1 000 mL加三乙胺10 mL,磷酸调pH至2.9)-甲醇(95∶5),流速为1.0 mL/min,柱温为35℃,检测波长为210 nm。结果主峰与相邻杂质峰能完全分离,质量浓度为1.003 6～20.072 g/L时与峰面积呈良好的线性关系(r=0.999 8,n=5);平均回收率为99.71%,RSD为1.26%(n=9);最低检测限为0.038 88 g/L。结论方法简单、灵敏、专属性强、结果准确,适用于测定盐酸丙酰左卡尼汀的有关物质和含量。     

盐酸丙酰左卡尼汀有关物质的合成研究

目的 为了更好的控制盐酸丙酰左卡尼汀产品的质量,建立健全盐酸丙酰左卡尼汀原料药的质量标准。方法 根据盐酸丙酰左卡尼汀的合成路线及工艺条件,分析并合成了原料药中可能存在的4种有关物质并经¹H-NMR、MS等进行了结构确证。结果 合成了盐酸丙酰左卡尼汀中存在的4种有关物质,为以后合成建立药物质量标准所需对照品提供了参考。结论各个有关物质的合成方法所用起始原料经济、简单易得,收率较高,所得产品纯度较高,合成工艺简便、条件温和、易于操作,合成路线可行。     

盐酸丙酰左卡尼汀中有机溶剂残留的毛细管GC测定

建立毛细管气相色谱法测定盐酸丙酰左卡尼汀中甲醇、丙酮、二氯甲烷3种有机溶剂的残留量.采用Agilent DB-WAX毛细管柱;FID检测器;程序升湿以30℃保持4min后,以10℃·min-1的升温速率升至60℃,再以40℃·min-1的升温速率升至220℃,终止时间3min;进样口温度180℃.本法灵敏、准确,适用于盐酸丙酰左卡尼汀中有机残留量的检测.     

酶化学法测定盐酸乙酰左卡尼汀片中盐酸乙酰左卡尼汀的含量

目的建立酶化学法测定盐酸乙酰左卡尼汀片中盐酸乙酰左卡尼汀含量的方法。方法采用卡尼汀乙酰转移酶、苹果酸脱氢酶、柠檬酸合成酶产生还原型辅酶Ⅰ(NADH),其增加的量与盐酸乙酰左卡尼汀的量成正比,根据NADH在340 nm的波长处有最大吸收的特点,测定盐酸乙酰左卡尼汀的含量。结果盐酸乙酰左卡尼汀的线性范围为13.48~53.92μg,线性方程为Y=0.967 2X-0.017 3,r=0.999 6,加样回收率为99.17%,RSD为1.06%(n=6)。结论该方法灵敏度高,专一性强,可用于盐酸乙酰左卡尼汀片中盐酸乙酰左卡尼汀的含量测定。     

丙酰左卡尼汀的基础研究和临床应用

<正>丙酰左卡尼汀(propionyl levo carnitine,PLC)为左卡尼汀乙酰转移酶刺激剂,能扩张外周微动脉血管,改善微循环。主要用于治疗或改善间歇性跛行状态,还可用于外周动脉病变疾病,同时它还具有延缓某些药物细胞毒性进程的作用。现将最新研究作一综述。     

高效液相色谱法测定左卡尼汀原料中的有关物质

目的建立HPLC法测定左卡尼汀中有关物质。方法采用Thermo APS-2 HYPERSIL色谱柱(250 mm×4.6 mm,5μm),流动相为磷酸盐缓冲液(含磷酸二氢钾质量浓度为6.81 g·L~(-1),用氢氧化钠试液调节pH值至4.7)-乙腈(体积比为35∶65);检测波长为205 nm;柱温为30℃;流速为1m L·min~(-1)。结果左卡尼汀和杂质A得到有效分离,分离度>1.5,流动相不干扰测定;左卡尼汀的检出限和定量限分别为15μg·L~(-1)和50μg·L~(-1),左卡尼汀杂质A的检出限为0.19μg·L~(-1);杂质A在质量浓度0.95~47.5μg·L~(-1)内线性关系良好(r=0.999 3)。结论建立的方法可用于左卡尼汀原料中有关物质的测定。     

UPLC法测定注射用左卡尼汀含量

目的 UPLC法测定注射用左卡尼汀含量,缩短检验周期,提高检验效率.方法 利用超高效液相色谱法,BEH C18色谱柱(50×4.6mm,1.7μm,waters公司),乙腈-磷酸氢二铵缓冲溶液(16:84)为流动相,柱温为35℃;流速0.3mL·min-1,检测波长为225nm.结果 左卡尼汀在质量浓度0.8~1.2mg·mL-1范围内线性关系良好(r=0.9995),平均回收率为99.8%.结论 本方法 简单、快速、准确,可用于注射用左卡尼汀的含量测定.     

左卡尼汀氯化钠注射液中左卡尼汀的含量测定

目的：建立高效液相色谱法测定左卡尼汀氯化钠注射液中左卡尼汀的含量。方法：采用Hypersil C18(4.6 mm×250 mm，10 μm)色谱柱，11 mg·mL 1庚烷磺酸钠甲醇溶液－0.05 mol·L 1磷酸二氢钾缓冲溶液(pH＝2.4)(5∶95)为流动相，流速1.0 mL·min 1，检测波长224 nm。结果：左卡尼汀在0.1～4.0 mg·mL 1浓度范围内线性关系良好(r＝0.999 8)。平均回收率(100.21±0.99)%，RSD＝0.98%。结论：该方法专属性好，简捷，快速，准确，适用于该产品的含量测定和质量控制。     

Rheological activity of propionyl L-carnitine

The authors have evaluated the efficacy of chronic administration of propionyl l-carnitine versus Buflomedil chlorhydrate in patients affected by vasculopathies. Patients were divided into two groups, A (n = 14) and B (n = 7); a third group C (n =7) was a control group of normal subjects. Groups A and C received 500 mg tablets of propionyl l-carnitine orally t.i.d. for 20 days. Group B received 40 mg of Buflomedil chlorhydrate i.v., b.i.d. for the same treatment period. Several blood cell viscosity parameters were evaluated. At the end of the trial it was possible to detect in the propionyl l-carnitine treated group a statistically significant decrease in haematic filtration time (HFT) and an increase in red blood cell flow velocity (Vrbc). Furthermore, some important rheological properties were noted, as demonstrated by modifications in the whole blood filtration, red blood cell flow velocity and viscosity of platelet-rich plasma following the addition of ADP.     

A randomised, controlled clinical trial evaluating changes in therapeutic efficacy and oxidative parameters after treatment with propionyl L-carnitine in patients with peripheral arterial disease requiring haemodialysis

OBJECTIVE: We explored the efficacy of intravenous therapy with propionyl L-carnitine in patients with both peripheral arterial disease (PAD) and chronic renal insufficiency requiring haemodialysis. METHODS: The trial was a randomised, double-blind, placebo-controlled trial. Sixty-four patients on haemodialysis (32 per treatment arm) with chronic renal insufficiency and PAD were assigned to receive either intravenous propionyl L-carnitine 600 mg or placebo 3 times weekly for 12 months. The main outcome measures were the ankle/brachial index (ABI), plasma malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) concentrations, and the plasma nitrite/nitrate ratio (NO(2)/NO(3)); these were measured at baseline and at 6 and 12 months. RESULTS: Significant increases in ABI were observed in the propionyl L-carnitine group, whereas in the placebo group the reverse trend was seen. In patients treated with propionyl L-carnitine, significant progressive decreases were seen in plasma MDA, 4-HNE and the NO(2)/NO(3) ratio from baseline. In the placebo-treated group, only weakly significant or no differences were seen. CONCLUSION: Intravenous administration of propionyl L-carnitine to haemodialysis patients with PAD improves both haemodynamic flow and the oxidative profile.     

“左旋肉碱减肥”没证据

前段时间,什么减肥药最火?大大小小的网站上,"左旋肉碱"的广告都在抢夺人们的视线。这种由某位"专家"现身说法的新型减肥药,是不是真能成为胖懒人的福音呢?     

Pharmacokinetics of L-carnitine

L-Carnitine is a naturally occurring compound that facilitates the transport of fatty acids into mitochondria for beta-oxidation. Exogenous L-carnitine is used clinically for the treatment of carnitine deficiency disorders and a range of other conditions.In humans, the endogenous carnitine pool, which comprises free L-carnitine and a range of short-, medium- and long-chain esters, is maintained by absorption of L-carnitine from dietary sources, biosynthesis within the body and extensive renal tubular reabsorption from glomerular filtrate. In addition, carrier-mediated transport ensures high tissue-to-plasma concentration ratios in tissues that depend critically on fatty acid oxidation. The absorption of L-carnitine after oral administration occurs partly via carrier-mediated transport and partly by passive diffusion. After oral doses of 1-6g, the absolute bioavailability is 5-18%. In contrast, the bioavailability of dietary L-carnitine may be as high as 75%. Therefore, pharmacological or supplemental doses of L-carnitine are absorbed less efficiently than the relatively smaller amounts present within a normal diet.L-Carnitine and its short-chain esters do not bind to plasma proteins and, although blood cells contain L-carnitine, the rate of distribution between erythrocytes and plasma is extremely slow in whole blood. After intravenous administration, the initial distribution volume of L-carnitine is typically about 0.2-0.3 L/kg, which corresponds to extracellular fluid volume. There are at least three distinct pharmacokinetic compartments for L-carnitine, with the slowest equilibrating pool comprising skeletal and cardiac muscle.L-Carnitine is eliminated from the body mainly via urinary excretion. Under baseline conditions, the renal clearance of L-carnitine (1-3 mL/min) is substantially less than glomerular filtration rate (GFR), indicating extensive (98-99%) tubular reabsorption. The threshold concentration for tubular reabsorption (above which the fractional reabsorption begins to decline) is about 40-60 micromol/L, which is similar to the endogenous plasma L-carnitine level. Therefore, the renal clearance of L-carnitine increases after exogenous administration, approaching GFR after high intravenous doses.Patients with primary carnitine deficiency display alterations in the renal handling of L-carnitine and/or the transport of the compound into muscle tissue. Similarly, many forms of secondary carnitine deficiency, including some drug-induced disorders, arise from impaired renal tubular reabsorption. Patients with end-stage renal disease undergoing dialysis can develop a secondary carnitine deficiency due to the unrestricted loss of L-carnitine through the dialyser, and L-carnitine has been used for treatment of some patients during long-term haemodialysis. Recent studies have started to shed light on the pharmacokinetics of L-carnitine when used in haemodialysis patients.     

HPLC法测定左卡尼汀氯化钠注射液中左卡尼汀的含量

目的 建立测定左卡尼汀氯化钠注射液含量的HPLC法.方法 采用Diamonsil C18(200mm×4.6mm,5μm)色谱柱,以庚烷磺酸钠-磷酸盐缓冲液-乙腈(555mg:955ml:55ml)为流动相,检测波长为225nm,流速1ml/min.结果 左卡尼汀在200～2000ng范围内线性关系良好(r=0.9998),平均回收率为97.88%,RSD为1.07%.结论 本方法快速、准确,可用于注射用左卡尼汀的含量测定.     

左卡尼汀的临床应用进展

本文主要介绍了左卡尼汀的药代动力学、药理作用及临床应用,为临床医生合理使用左卡尼汀提供参考。     

Antinociceptive activity of propionyl esters of morphine: a reevaluation

The antinociceptive activity of the propionyl homologues of 3-O- and 6-O-acetyl- and 3,6-O-diacetylmorphine was re-investigated using materials of unequivocally established structure. Testing was in male Wistar rats at 60 min following subcutaneous administration by the rat tail-flick method. Results indicate that the antinociceptive activity of 3-O-propionylmorphine was similar to that of 3-O-acetylmorphine. 6-O-Propionylmorphine and 3,6-O-dipropionylmorphine had similar antinociceptive activity and, like 6-O-acetylmorphine, 6-O-propionylmorphine may be the pharmacologically active principle responsible for the antinociceptive activity of its disubstituted homologue.