高效液相色谱法测定盐酸坦洛新中S异构体的含量

目的 建立测定盐酸坦洛新中S异构体含量的高效液相色谱法.方法 采用Daieel Chiralcel OD-RH柱(250mm×4.6 mm,5μm)为色谱柱,流动相为乙腈-pH值为4.0的0.8 mol/L高氟酸钠溶液(25:75),流速0.5 mL/min,检测波长224 nm,柱温30℃.结果 盐酸坦洛新R异构体与S异构体的分离度达2.0,S异构体的线性范围为0.4995-7.992μg/mL(r=0.9998),平均回收率为98.7%(n=9).结论 高效液相色谱法操作简便,灵敏精确,可用于盐酸坦洛新中S异构体的含量测定.     

HPLC法测定地红霉素肠溶微丸的有关物质

目的:测定地红霉素肠溶微丸的有关物质.方法:采用HPLC法,色谱柱为DiamonsilTM C18(250 mm×4.6 mm,5μm);流动相为乙腈-磷酸盐缓冲液(取磷酸二氢钾1.41 g,磷酸氢二钾6.91 g,加水至1 000 mL)-甲醇(44:37:19);柱温40℃;检测波长为205 am,流速2.0 mL·min-1.结果:此色谱条件下药物与降解产物能达有效分离,地红霉素16R异构体与地红霉素16S异构体的分离度≥2.0;地红霉素16R异构体与9(S)红霉胺的分离度≥5.0.结论:本法简便,准确,方法可行.     

HPLC法检测盐酸戊乙奎醚R型异构体经小鼠尿排泄的方法学研究

目的 :建立HPLC测定方法研究R型盐酸戊乙奎醚光学异构体在小鼠体内的排泄。方法 :采用新建立的正相HPLC法 ,尿样经提取处理后 ,选用SpherisorbSiO2 色谱柱 ,以甲醇 二氯甲烷 氨水 (8 2 0 .1)为流动相 ,流速 0 .8ml·min-1,检测波长2 5 4nm ,进样量 2 0 μl。结果 :在 0 .5～ 10 0mg·L-1浓度范围内 ,R异构体峰面积与浓度呈良好的线性关系 (r分别为 0 .9994与 0 .9997)。两R型异构体的平均回收率均大于 85 % ,日内和日间RSD均小于13%。小鼠肌注给药后不同时间内 ,R型异构体在尿中的比值 (R 1 R 2 )存在显著差异 (P <0 .0 5 )。4 8h内R型异构体在尿中的排泄量明显不同。结论 :本法简单方便 ,可用于R型异构体在小鼠体内立体选择性排泄研究。     

HPLC-MS法测定甲磺酸多拉司琼原料药中有关物质和异构体含量

目的:建立甲磺酸多拉司琼原料药中有关物质和异构体含量测定的方法。方法:采用高效液相色谱-质谱法测定3批甲磺酸多拉司琼原料药中的有关物质和异构体含量。色谱柱为shim-packVP-ODS;流动相A为0.01mol·L-1甲酸铵溶液(用三乙胺调m节inp-H1;至检7测.0)波-乙长腈为(29150∶5n)m,。流质动谱相条B件为采0.0用1电mo喷l.雾L-电1甲离酸源铵(E溶S液I)(、正用离三子乙检胺测调节模式pH。至结7果.0):-有乙效腈(分2离7∶了73)甲,磺梯酸度多洗拉脱司,流琼速与为有1关.0物mL质.及异构体(R>1.5),甲磺酸多拉司琼的最低检测限为0.5ng,3批样品中单个杂质含量≤0.05%,总杂质含量<0.1%,异构体未检出。结论:本方法准确、专属性好,适用于甲磺酸多拉司琼原料药中有关物质和异构体的检测。     

HP-β-CD手性添加剂反相高效液相色谱拆分盐酸帕洛诺司琼S,R异构体

目的:以HP-β-环糊精为手性流动相添加剂,在RP-HPLC模式下建立盐酸帕罗诺司琼的异构体分析方法方法:采用资生堂CAPCELL PAK C18VG120(250 mm×4.6 mm,5μm)色谱柱,流动相为三乙胺(TEA)与不同浓度羟丙基-β-环糊精混合,通过乙酸调节p H,检测波长240 nm,柱温30℃,通过优化不同浓度的羟丙基-β-环糊精与p H,及流速,优化最佳分离条件。结果:最终确定以0.5%三乙胺(1%羟丙基-β-环糊精,用乙酸调节p H至5.5)-乙腈(85∶15)为流动相,流速0.5 ml·min-1,进样量10μl的色谱条件作为分离手段。盐酸帕罗诺司琼S,R异构体与主成分在手性添加剂作为流动相条件下分离良好。结论:该方法可以作为盐酸帕罗诺司琼光学异构体检查控制方法。     

HPLC法测定米格列奈钙中的R-异构体含量

目的:采用高效液相色谱法测定米格列奈钙中的R-异构体的含量.方法:使用Sumichiral OA-3100R手性色谱柱,流动相为正己烷-氯仿-甲醇-三氟乙酸(80:18:2:0.5),流速 1.0 mL·min -1,检测波长 259 nm,柱温35℃,进样量 20 μL,并考察了流动相组成、柱温和流速等色谱条件对分离的影响. 结果:米格列奈钙与R-异构体,分离度为2.26,理论塔板数为5165.结论:该法简便,准确,能有效地进行米格列奈钙中的R-异构体的定量分析.     

1H核磁共振定量法用于25(R,S)-鲁斯可皂苷元及其光学异构体的含量研究

目的:建立25(R,S)-鲁斯可皂苷元及其光学异构体的¹H核磁共振定量法(¹H qNMR)含量测定方法。方法:采用外标法,以鲁斯可皂苷元对照品为对照,分别以δ 5.42、3.45和3.79处的信号为25(R,S)-鲁斯可皂苷元、25R鲁斯可皂苷元和25S鲁斯可皂苷元的定量峰,以δ 6.63处的信号为内标富马酸的定量峰进行校准,对25(R,S)-鲁斯可皂苷元及其光学异构体进行定量研究。结果:25(R,S)-鲁斯可皂苷元的含量分别为97.88%(RSD=0.93%,n=5),与外标法(97.88%)、质量平衡法(97.98%),紫外分光光度法(98.40%)基本一致;25R-鲁斯可皂苷元含量为49.63%(RSD=1.5%,n=5)和25S-鲁斯可皂苷元含量为46.47%(RSD=1.5%,n=5),测定结果之和与25(R,S)-鲁斯可皂苷元总量基本一致。结论:¹H qNMR方法简便易行,可用于25(R,S)-鲁斯可皂苷元及其光学异构体的含量测定,为光学异构体的含量测定提供了新的技术方法;同时开展了外标法核磁定量测定方法的研...     

大鼠血浆中抗精神分裂症候选新药SIPI6360立体异构体的LC-MS/MS法测定

建立了液相色谱-串联质谱法拆分并测定大鼠血浆中SIPI6360的立体异构体.采用Daicel Chiralpak IA手性柱,以甲醇为流动相,采用ESI源正离子模式、多反应监测进行定量分析.结果显示,(R)-(+)-SIPI6360与(S)-(-)-SIPI6360立体异构体分离良好,在0.5～100 ng/ml浓度范围内线性关系良好.方法回收率为94.0％～102.8％,批内和批间RSD小于5.2％和11.4％.     

茚喹诺啉对映体的手性拆分及转化研究

目的:建立茚喹诺啉[(1S/R,1’S/R)-1-(四氢吡咯-1-甲基)-2-(6-氯-2,3-二氢-茚-3-酮-1-羰基)-1,2,3,4-四氢异喹啉]对映体的高效液相色谱拆分方法并研究它的对映体转化。方法:采用Chiralcel OD-RH(150 mm×4.6mm,5.0μm,Daicel公司)手性色谱柱在反相条件下直接拆分茚喹诺啉对映体,考察了流动相pH和比例等对茚喹诺啉对映体分离的影响。确定了较佳的拆分流动相条件为0.05 mol.L-1磷酸二氢钾缓冲溶液(磷酸调pH2.5)-乙腈(70∶30,v/v)。结果:发现具有两手性中心的茚喹诺啉在非不对称合成条件下仅生成SS和RR2种光学异构体;在给质子溶剂如甲醇或水溶液中,尤其在加热或碱催化下,由于茚-3-酮-1-羰基的手性碳存在明显的消旋化,可生成4个光学异构体。结论:茚喹诺啉的4种光学异构体可在Chiralcel OD-RH手性色谱条件下获得良好的分离和检测,可用于其制备控制和质量检验。     

那格列奈及其片剂中L-异构体的HPLC测定

建立了HPLC法测定那格列奈及其片剂中的杂质L-异构体的含量.采用以α-酸性糖蛋白键合硅胶为固定相的手性色谱柱,0.02mol/L磷酸钾缓冲液(pH 7.1)-乙腈(98:2)为流动相,检测波长210nm,L-异构体检测限为2ng,平均回收率为98.0%.     

Pharmacokinetics of palonosetron in combination with aprepitant in healthy volunteers

BACKGROUND: Palonosetron is a second-generation 5-HT(3) receptor antagonist with a prolonged duration of action and higher receptor binding affinity than first-generation agents (ondansetron, granisetron, and dolasetron). Aprepitant is a selective antagonist of substance P/neurokinin 1 that augments the benefit of 5-HT(3) receptor antagonists in the prevention of chemotherapy-induced nausea and vomiting. METHODS: This randomized, open-label, two-way, crossover trial was designed to evaluate the effect of oral aprepitant on the pharmacokinetics and safety of a single intravenous (IV) dose of palonosetron in 12 healthy subjects. Treatment A consisted of a single IV bolus dose of palonosetron 0.25mg on day 1. Treatment B added oral aprepitant 125 mg on day 1 (30 minutes prior to palonosetron) and 80 mg on days 2 and 3. Blood for pharmacokinetic evaluations was collected through 168 hours after palonosetron administration on days 1 and 15; safety was monitored through day 22. RESULTS: Mean plasma concentration-time plots for palonosetron were virtually identical for palonosetron administered alone or with concomitant aprepitant. The ratio of geometric least-square mean values (with:without aprepitant) for C(max) was 98.6% (90% confidence interval [CI]: 61.8-157%), and for AUC(0-infinity) the ratio was 101% (90% CI: 85.6-119%). With and without aprepitant coadministration, respectively, mean plasma elimination half-life was 40 hours and 43 hours (difference: -3.0 hours; p = 0.348), mean total body clearance was 130 mL/min and 136 mL/min (difference: -5.6 mL/min; p = 0.735), and mean volume of distribution at steady-state was 410.9 L and 442.3 L (difference: -31.4 L; p = 0.463). Palonosetron alone and the palonosetron/aprepitant regimen were well tolerated. CONCLUSION: These results indicate no significant differences in pharmacokinetic parameters for palonosetron between the two treatments, and suggest that palonosetron can be safely coadministered with aprepitant with no alterations in the expected safety profile and no dosage adjustment necessary.     

Pharmacokinetic and safety evaluation of palonosetron, a 5-hydroxytryptamine-3 receptor antagonist, in U.S. and Japanese healthy subjects

Palonosetron (Aloxi, Onicit) is a selective 5-HT(3) receptor antagonist recently approved by the Food and Drug Administration for the prevention of acute and delayed chemotherapy-induced nausea and vomiting. This study was performed to determine the pharmacokinetics and assess the safety and tolerability of intravenous (IV) palonosetron in healthy U.S. and Japanese subjects. Subjects were administered a single IV dose of palonosetron, ranging from 0.3 to 90 microg/kg in either of two randomized, double-blind, placebo-controlled, ascending-dose studies (n = 80 and n = 32, respectively). Serial blood samples were obtained in both studies to evaluate the pharmacokinetics of palonosetron and its N-oxide metabolite, M9. Intravenous palonosetron was well tolerated across a wide range of doses in both studies. The incidence and severity of adverse events (AEs) were similar between subjects receiving palonosetron and those receiving placebo, with no dose-dependent incidences. The most frequently reported AEs were headache, transient elevation of liver enzymes, and constipation. Systemic exposure (AUC and C(max)) for palonosetron generally increased with increasing dose. Mean total body clearance, elimination half-life, and apparent volume of distribution ranged from 1.11 to 3.90 mL/min/kg, 33.7 to 54.1 hours, and 3.85 to 12.6 L/kg, respectively, in U.S. subjects and from 2.58 to 3.50 mL/min/kg, 30.8 to 36.8 hours, and 6.96 to 9.85 L/kg, respectively, in Japanese subjects. The pharmacokinetics of palonosetron appeared to be independent of dose, with no dose adjustment required in Japanese subjects. The plasma concentration profile of palonosetron, as represented by a half-life of approximately 40 hours, may provide a clinical advantage over other 5-HT(3) antagonists.     

3种止吐药物在晚期食管癌患者化疗中的药物经济学评价

目的：前瞻性研究本院帕洛诺司琼、阿扎司琼和托烷司琼对化疗引起恶心和呕吐的影响及对不同止吐方案进行成本-效果分析。方法：选取2018年1月~2019年12月间124例采用多西他赛+顺铂（DP）方案化疗的晚期食管癌患者作为研究对象,均签署知情同意书。将其随机分为3组（帕洛诺司琼组、阿扎司琼组和托烷司琼组）。在化疗前,分别给予相应药物预防止吐,通过MAT量表与FLIE量表对化疗相关恶心呕吐（CINV）情况进行评估,并基于医疗提供者角度,开展成本-效果分析。结果：3组抑制急性呕吐与恶心、延迟性呕吐与恶心方面,疗效比较无统计学差异（P>0.05）。住院期间抑制呕吐与恶心的药物成本,三种方案有统计学差异（P<0.05）。采用最小成本法,帕洛诺司琼成本最低,具有经济性。敏感性分析结果显示：缓解恶心和呕吐,帕诺洛司琼具有经济性概率始终最高。结论：帕诺洛司琼具有较好的经济性。     

反相高效液相色谱法检测盐酸帕洛诺司琼的有关物质

目的建立测定盐酸帕洛诺司琼有关物质的反相高效液相色谱（RP-HPLC）法。方法色谱柱为Shim-packVP-ODS柱（150mm×4.6mm,5μm）,流动相A为0.02mol/L磷酸二氢钾溶液（用磷酸调节pH至2.5）-乙腈（90∶10）,流动相B为0.02mol/L磷酸二氢钾溶液（用磷酸调节pH至2.5）-乙腈（60∶40）,梯度洗脱,流速1.0mL/min,检测波长210nm。结果在此色谱条件下,盐酸帕洛诺司琼与杂质及降解产物可以有效分离。结论 RP-HPLC法准确、专属性好,适用于盐酸帕洛诺司琼有关物质及降解产物的检测。     

盐酸帕洛诺司琼3个光学异构体的分离与测定

目的:建立盐酸帕洛诺司琼中3个异构体的分离和含量测定方法。方法:采用以替考拉宁手性柱CHIROBIOTIC TTM(250 mm×4.6 mm,5μm),流动相为甲醇-冰醋酸-三乙胺(100:0.5:0.3),流速:0.5 mL·min-1;检测波长:238 nm。结果:盐酸帕洛诺司琼与3个异构体分离良好,保留适宜;3个异构体在2μg·mL-1至20μg·mL-1范围内,线性良好(r=0.9992～0.9999),进样精密度良好(RSD=0.88%～1.7%,n=5)。结论:方法专属性好、精密度高,适用于盐酸帕洛诺司琼异构体的测定。     

盐酸帕洛诺司琼预防化疗药物所致胃肠道反应63例

目的 观察盐酸帕洛诺司琼预防化疗药物所致胃肠道反应的疗效和安全性,并与盐酸托烷司琼进行对比. 方法采用随机自身交叉对照,63例入选患者分为AB组32例和BA组31例,AB组第1周期应用盐酸帕洛诺司琼,第2周期应用盐酸托烷司琼;BA组则相反. 结果 可评价患者63例,化疗后0～24 h盐酸帕洛诺司琼和盐酸托烷司琼对化疗引起的食欲不振 、恶心和呕吐的有效率相似,在24～120 h和0～120 h,盐酸帕洛诺司琼对化疗引起的食欲不振 、恶心和呕吐的有效率优于盐酸托烷司琼,差异有统计学意义(P<0.05). 两药的不良反应相似,主要为头痛和便秘. 结论 盐酸帕洛诺司琼对延迟性恶心呕吐的有效性优于盐酸托烷司琼,值得临床推广应用.     

Pharmacokinetics, metabolism and excretion of intravenous [l4C]-palonosetron in healthy human volunteers

Palonosetron (Aloxi(R), Onicit(R)) is a potent, single stereoisomeric 5-HT(3) receptor antagonist developed to prevent chemotherapy-induced nausea and vomiting. The pharmacokinetics and metabolic disposition of a single intravenous [(14)C]-palonosetron (10 microg/kg, 0.8 microCi/kg) bolus dose were evaluated in six healthy volunteers (three males, three females) using serial blood, plasma, urine and fecal samples obtained over 10 days. The safety, tolerability and cardiac effects were assessed. Radiolabeled metabolic characterization revealed that unchanged palonosetron accounted for 71.9% of the total radioactivity in plasma over 96 h, with an extensive distribution volume (8.34 l/kg) and mean plasma elimination half-life of 37 h. Approximately 83% of the dose was recovered in urine ( approximately 40% as unchanged drug, with 50% metabolized; M9 and M4 were the major metabolites) and 3.4% in feces. Hydrolysis of urine samples suggests that the metabolites are not beta-glucuronide or sulfate conjugates of the parent drug or metabolites. The blood to plasma concentration ratio of the total radioactivity was 1.2, on average, indicating little selective partitioning in erythrocytes. Palonosetron was generally well tolerated; headache was the most frequently reported adverse event. Electrocardiograms and 72 h Holter monitoring revealed no clinically significant changes. Palonosetron circulates in plasma mainly as the parent drug. Renal elimination is the primary excretion route, with parent drug and metabolites M9 and M4 accounting for the majority of palonosetron disposition. These results indicate that both renal and hepatic routes are involved in the elimination of palonosetron from the body.     

Compatibility of palonosetron with cyclophosphamide and with ifosfamide during simulated Y-site administration.

PURPOSE: The physical and chemical compatibility of palonosetron with cyclophosphamide and with ifosfamide during simulated Y-site administration was studied. METHODS: Test samples were prepared in triplicate by mixing 7.5 mL of palonosetron hydrochloride 50 microg (of palonosetron) per milliliter with 7.5 mL of cyclophosphamide 10 mg/mL and with ifosfamide 20 mg/mL. Physical stability was assessed by turbidimetry, particle sizing, and visual inspection. Chemical stability was assessed by stability-indicating high-performance liquid chromatography. Evaluations were performed immediately and one and four hours after mixing. RESULTS: The samples were clear and colorless when viewed in normal fluorescent room light and when viewed with a high-intensity monodirectional light. Turbidity remained unchanged, and particulate content was low and exhibited little change. Palonosetron, cyclophosphamide, and ifosfamide remained chemically stable throughout the four-hour test period. CONCLUSION: Palonosetron hydrochloride was physically compatible with cyclophosphamide or ifosfamide during simulated Y-site administration.     

HPLC method for the determination of ecdysterone in extractive solution from Pfaffia glomerata

A RP-LC method was developed and validated to quantify ecdysterone in extractive solution from subterraneous parts of Pfaffia glomerata. The analysis was performed using a RP-18 column with acetonitrile:water isocratic elution and the detection was carried out by UV at 242 nm. The standard curve for ecdysterone was linear over the range of 5.2-41.6 microg/ml (R2=0.9995). The extractive solution showed linear response in the range of 25.05-175.35 microg/ml (R2=0.9977). This method showed excellent repeatability (relative standard deviation, R.S.D.<2.0%), intermediary precision (R.S.D.=2.13%) and accuracy (101.04; R.S.D.=1.51%). The limit of detection (LOD) was 0.036 microg/ml and the limit of quantification (LOQ) was 0.110 microg/ml, demonstrating the sensitivity of the method. This assay can be readily utilized as quality controlled method for P. glomerata preparations.     

Different doses of palonosetron for the prevention of postoperative nausea and vomiting in children undergoing strabismus surgery

Objective: The aim of this study was to evaluate the efficacy of different doses of palonosetron for the prevention of PONV in children undergoing strabismus surgery.Patients and Method: A total of 150 children who were classified with an American Society of Anesthesiologists physical status of I, were aged between 2 and 12 years, and were undergoing strabismus surgery under general anesthesia were enrolled in the study. A random numbers table was used to assign each child to receive palonosetron 0.5, 1.0, or 1.5 μg/kg (n = 50 in each group).All episodes of PONVat the intervals of 0–2, 2–6, 6–24, and 24–48 hours were evaluated using a numeric scoring system for PONV. A p-value of <0.05 was considered statistically significant.Results: The percentage of children with PONV during 0–48 hours after anesthesia was 24% with palonosetron 0.5 or 1.0 μg/kg, and 20% with palonosetron 1.5 μg/kg. There was no statistically significant difference between the study groups with respect to the number of children with PONV scores of 1, 2, or 3 during 0–48 hours after anesthesia. There was no statistically significant difference between the study groups with respect to the number of children with postoperative vomiting during all time periods after anesthesia. The percentage of children aged >6 years with postoperative nausea during 0–48 hours after anesthesia was 8.6%, 18.2%, and 15.4% with palonosetron 0.5, 1.0, or 1.5 μg/kg, respectively, but there was no statistically significant difference between the study groups.Conclusion: Palonosetron doses of 0.5, 1.0, and 1.5 μg/kg are recommended for further evaluation, as they appear to be the effective doses for the prevention of PONV following strabismus surgery in children.