高效液相色谱法测定注射用头孢他啶有关物质

目的建立注射用头孢他啶有关物质的高效液相测定方法.方法采用ZorbaxSB-C18色谱柱(5μm,4.6×150mm),以乙腈-pH7.0磷酸盐缓冲液-水(40∶200∶1760)以流动相,检测波长254nm.结果头孢他啶主峰与各杂质峰分离度好.结论本法快速、准确、适用于该产品的有关物质考察.     

A simple formula for individualising ceftazidime dosage administered by continuous infusion in patients with haematological malignancies

A formula is proposed for individualising ceftazidime dosage administered by continuous infusion in patients with haematological malignancies. Sixty patients were retrospectively randomised into Group A (n = 30) to establish the formula and Group B (n = 30) to evaluate this formula. Individual ceftazidime clearances were estimated from the ratio between the rate of infusion and plasma concentration at steady state. In Group A, ceftazidime clearance was significantly correlated with creatinine clearance. From this result, a formula (rate of infusion (g/day) = 0.00133 × [creatinine clearance (mL/min)] × [target concentration at steady state (mg/L)]) is proposed. This formula provided consistent estimations of ceftazidime plasma concentrations in Group B and should help clinicians to define the optimum ceftazidime dosage, particularly in patients with disturbed renal function.     

HPLC法测定注射用盐酸头孢吡肟中2-巯基苯并噻唑

摘要：目的 建立HPLC法测定注射用盐酸头孢吡肟中2-巯基苯并噻唑基因毒性杂质含量的方法。方法 HPLC法,采用 Inertsil ODS-3柱(250 mm×4.6 mm,5 μm),以50 mmol/L磷酸氢二钠溶液(用磷酸调pH值至6.25)-甲醇-80%乙腈(60:10:30, V/V/V) 为流动相,等度洗脱,流速为1 mL/min,柱温为35℃,检测波长为320 nm,进样体积为10 μL。结果 2-巯基苯并噻唑在浓度 0.01~102.9 μg/mL范围内,呈良好的线性关系,回归方程y= 70652x+2167.2,相关系数r=0.9999;定量限为0.3 ng,检测限为 0.1 ng, 回收率均值(n=9)为91.7%。结论 本方法专属性强、准确、快捷、灵敏且耐用性良好,为测定注射用盐 酸头孢吡肟中2-巯基苯 并噻唑含量的有效补充检测与定量方法,并为该产品临床应用安全性提供保障。     

高效液相色谱法测定头孢他啶与3种输液配伍的稳定性实验

目的:测定头孢他啶与三种输液配伍的稳定性,为临床用药提供依据。方法:高效液相色谱法。结果:头孢他啶与三种输液的配伍在室温和冰箱保存２４ ｈ、２８ ｈ含量大于９８%,放置４８ ｈ后也均大于９６%。结论:头孢他啶与三种输液配伍在室温和冰箱均稳定。     

RP-HPLC考察注射用盐酸头孢吡肟与氟康唑氯化钠注射液配伍的稳定性

目的考察室温(20±1)℃下,注射用盐酸头孢吡肟与氟康唑氯化钠注射液配伍的稳定性。方法采用反相高效液相色谱法测定配伍液中头孢吡肟与氟康唑0～6 h内的含量变化,并观察配伍液的外观及pH值。结果注射用盐酸头孢吡肟与氟康唑氯化钠注射液6 h内配伍液外观、pH值及含量均无明显变化。结论在室温(20±1)℃下,注射用盐酸头孢吡肟与氟康唑氯化钠注射液配伍后6 h内可使用。     

HPLC法测定人血浆中头孢吡肟的浓度

目的:建立以高效液相色谱法测定人血浆中头孢吡肟浓度的方法。方法:色谱柱为DiamonsilC18,流动相为20mmol.L-1醋酸铵溶液(冰醋酸调节pH值至5.00)-乙腈(90:10),流速为1.0mL.min-1,检测波长为254nm,进样量为20μL,柱温为室温。结果:头孢吡肟血药浓度在0.2～50.0μg.mL-1范围内线性关系良好(r=0.9996),定量下限为0.2μg.mL-1;平均方法回收率为99.16%(RSD=1.29%),平均提取回收率为85.43%(RSD=2.37%),日内、日间RSD均<10%。结论:本方法简便、灵敏、快速、准确,可用于人血浆中头孢吡肟的药动学和生物利用度研究。     

HPLC法测盐酸头孢吡肟精氨酸中头孢吡肟的含量

目的:用高效液相色谱法测定头孢吡肟含量。方法:ODS柱,以戊烷磺酸钠溶液-乙腈为流动相,于254nm波长处检测,流速为1．0ml／min。结果:该方法在80μg·ml-1-480μg·ml-1范围内峰面积与浓度呈良好的线性关系(r=0．9997),重复性实验RSD=0．59％,n=5。结论:方法简便,快速,重复性好。     

高效液相色谱法测定头孢他啶注射剂的含量

目的建立用高效液相色谱法测定头孢他啶注射剂含量的方法.方法以甲硝唑为内标,所用色谱柱为ODS柱,流动相为磷酸盐缓冲液(含0.08%NaH2PO4,pH=4.7)-甲醇＝9∶1,流速1.5ml*min-1,检测波长为254nm.结果在5.0～50.0μg*ml-1的浓度范围内具有良好的线性关系,r＝0.9999.平均回收率为100.6%,RSD＝0.79%.与中国药典2000年版方法相比,差异无显著性(P>0.05).结论采用内标法测定简便,快速,灵敏,准确.     

气相色谱法测定头孢吡肟中N-甲基吡咯烷杂质含量

目的　用顶空气相色谱法测定盐酸头孢吡肟中 N-甲基吡咯烷杂质含量。方法　顶空气相色谱法 ,采用 HP- 6 2 4毛细管柱 ,30 m× 0 .5 3mm;氢火焰检测器 ;柱温 :80℃ ;气化室温度 :2 5 0℃ ;检测器温度 :2 80℃ ;载气为氮气 ;内标物正丙醇。结果　 N-甲基吡咯烷浓度在 5× 10 - 5～ 2 .5× 10 - 4g时线性关系良好 ,线性方程为 A吡咯烷 / A内标 =9.17× 10 4 C+0 .5 78,相关系数为 r=0 .998;RSD(% ) =0 .76。平均回收率为 10 3% ;检测限为 1.2 2× 10 - 9g。结论　本方法简便、准确、适用性广 ,便于在生产过程中进行监控。     

气相色谱法测定头孢吡肟中N-甲基吡咯烷杂质含量

目的用气相色谱法测定盐酸头孢吡肟中N-甲基吡咯烷杂质含量。方法采用毛细管气相色谱法，氢火焰离子化检测器（FID）。弹性石英毛细管柱HP-1（60m×0．53mm．5μm）；柱温100℃；气化室温度250U；检测器温度250℃;载气为氮气;进样量1μl；分流比为10：1。结果N-甲基吡咯烷浓度在1．1213-134．56μg／ml时线性关系良好·线性方程；A吡咯烧／A内标=0.01561C-0．00854，相关系数r=0．999981RSD（％）=0．00486。加样回收率101．73％；检测限0．6ng。结论本法简便、准确、适用性广，便于在生产过程中进行监控。     

HPLC测定注射用盐酸头孢吡肟的含量

目的采用RP-HPLC法测定注射用盐酸头孢吡肟的含量。方法色谱柱为Kromasil C18柱(250 mm×4.6 mm,5μm),流动相为戊烷磺酸钠溶液-乙腈(96:4),流速1.0 ml.min-1,检测波长254 nm。结果盐酸头孢吡肟的线性范围为100.08~150.12μg.ml-1(r=0.9998);平均回收率为99.57%,RSD=0.27%(n=9)。结论所建方法快速、简便、准确、重复性好,可用于注射用盐酸头孢吡肟的含量测定。     

高效毛细管电泳法测定注射用盐酸头孢吡肟的含量

目的　测定注射用盐酸头孢吡肟的含量。方法　高效毛细管电泳法。毛细管 6 0 cm× 75 μm;运行缓冲液 30 mmol/ L 硼砂 (p H9.2 ) ,高压进样 5 s,分离电压 12 k V,温度为 2 5℃ ,检测波长为 2 5 4 nm,地塞米松磷酸钠为内标。结果　头孢吡肟在 6～ 30 μg/ ml浓度范围内线性关系良好 (r=0 .9998) ,平均回收率为 98.97%。结论　本法简单、快捷、灵敏。     

Determination of meropenem in plasma and filtrate-dialysate from patients under continuous veno-venous haemodiafiltration by SPE-LC

Meropenem, a carbapenem antibiotic displaying a broad spectrum of antibacterial activity, is administered in Medical Intensive Care Unit to critically ill patients undergoing continuous veno-venous haemodiafiltration (CVVHDF). However, there are limited data available to substantial rational dosing decisions in this condition. In an attempt to refine our knowledge and propose a rationally designed dosage regimen, we have developed a HPLC method to determine meropenem after solid-phase extraction (SPE) of plasma and dialysate fluids obtained from patients under CVVHDF. The assay comprises the simultaneous measurement of meropenem's open-ring metabolite UK-1a, whose fate has never been studied in CVVHDF patients. The clean-up procedure involved a SPE on C18 cartridge. Matrix components were eliminated with phosphate buffer pH 7.4 followed by 15:85 MeOH-phosphate buffer pH 7.4. Meropenem and UK-1a were subsequently desorbed with MeOH. The eluates were evaporated under nitrogen at room temperature (RT) and reconstituted in phosphate buffer pH 7.4. Separation was performed at RT on a Nucleosil 100-5 microm C18 AB cartridge column (125 x 4 mm I.D.) equipped with a guard column (8 x 4 mm I.D.) with UV-DAD detection set at 208 nm. The mobile phase was 1 ml min(-1), using a step-wise gradient elution program: %MeOH/0.005 M tetrabutylammonium chloride pH 7.4; 10/90-50/50 in 27 min. Over the range of 5-100 microg ml(-1), the regression coefficient of the calibration curves (plasma and dialysate) were >0.998. The absolute extraction recoveries of meropenem and UK-1a in plasma and filtrate-dialysate were stable and ranged from 88-93 to 72-77% for meropenem, and from 95-104 to 75-82% for UK-1a. In plasma and filtrate-dialysate, respectively, the mean intra-assay precision was 4.1 and 2.6% for meropenem and 4.2 and 3.7% for UK-1a. The inter-assay variability was 2.8 and 3.6% for meropenem and 2.3 and 2.8% for UK-1a. The accuracy was satisfactory for both meropenem and UK-1a with deviation never exceeding 9.0% of the nominal concentrations. The stability of meropenem, studied in biological samples left at RT and at +4 degrees C, was satisfactory with < 5% degradation after 1.5 h in blood but reached 22% in filtrate-dialysate samples stored at RT for 8 h, precluding accurate measurements of meropenem excreted unchanged in the filtrate-dialysate left at RT during the CVVHDF procedure. The method reported here enables accurate measurements of meropenem in critically ill patients under CVVHDF, making dosage individualisation possible in such patients. The levels of the metabolite UK-1a encountered in this population of patients were higher than those observed in healthy volunteers but was similar to those observed in patients with renal impairment under hemodialysis.     

头孢他啶在甲硝唑葡萄糖注射液中的稳定性

目的：本文模拟临床头孢他啶使用习惯，将头孢他啶加入甲硝唑葡萄糖注射液中静滴，研究其稳定性。方法：根据两种药物的pH范围，将甲硝唑葡萄糖注射液调整pH为4．51和6．06，后模拟临床用药剂量，取头孢他啶2g分别加入250mL上述两种液体中，混匀得Ⅰ、Ⅱ号液，取100灿加过滤蒸馏水稀释至10mL，进样20μL。用高效液相色谱法，在检测波长254nm，流动相5％甲醇，流速0．70mL-min^-1，灵敏度0．05AUFS，柱温20℃；25℃和35℃的条件下检测两种药物的稳定性。结果：两种药物在不同条件下、不同时间段药物浓度含量变化在±10％以内。结论：头孢他啶与甲硝唑葡萄糖注射液伍用，25℃、4h或35℃、2h，其含量变化不明显，pH略有下降，不影响用药安全、有效。     

HPLC法测定头孢他啶原料药及制剂中杂质头孢他啶叔丁酯的含量

目的:建立了测定头孢他啶原料药及注射用头孢他啶中杂质头孢他啶叔丁酯含量的方法。方法:采用高效液相色谱法。色谱柱为C18,流动相A、B分别为乙腈-pH7.0的磷酸盐缓冲溶液(7∶93)、(25∶75)溶液,线性梯度洗脱,检测波长为255nm。结果:头孢他啶叔丁酯检测浓度线性范围为0.01～1.22μg·μL-1,平均回收率为99.4%,RSD=1.0%。结论:该方法专属性强、快速、准确,可用于头孢他啶原料药及制剂中头孢他啶叔丁酯含量的测定。     

Simultaneous determination of vancomycin and ceftazidime in cerebrospinal fluid in craniotomy patients by high-performance liquid chromatography

A simple, accurate and rapid method for simultaneous analysis of vancomycin and ceftazidime in cerebrospinal fluid (CSF), utilizing high-performance liquid chromatography (HPLC), has been developed and thoroughly validated to satisfy strict FDA guidelines for bioanalytical methods. Protein precipitation was used as the sample pretreatment method. In order to increase the accuracy, tinidazole was chosen as the internal standard. Separation was achieved on a Diamonsil C18 column (200 mm x 4.6mm I.D., 5 microm) using a mobile phase composed of acetonitrile and acetate buffer (pH 3.5) (8:92, v/v) at room temperature (25 degrees C), and the detection wavelength was 240 nm. All the validation data, such as accuracy, precision, and inter-day repeatability, were within the required limits. The method was applied to determine vancomycin and ceftazidime concentrations in CSF in five craniotomy patients.     

反相高效液相色谱法分析测定头孢克洛

以磷酸盐缓冲液－甲醇为流动相在Ｃ１８柱上分离测定头孢克洛，检测波长２５４ｎｍ，乙酰苯胺作内标。ＣＣＬ进样量在０．４－２．４μｇ间线性关系良好，加样回收率９９．８％，重复进样的ＲＳＤ为０．３６％。     

固相萃取-高效液相色谱法测定人血清中头孢吡肟浓度

目的:建立高效液相色谱法检测人血清中头孢吡肟浓度。方法:血清经固相萃取后,在WatersSymmetryshieldRP18色谱柱上,以甲醇-20mmol·L-1醋酸铵溶液(13∶87)为流动相,流速1.0mL·min-1,波长检测254nm。结果:头孢吡肟的保留时间为6.82min,最低定量限为0.5mg·L-1,线性范围0.5~100.0mg·L-1,萃取回收率82.95%~86.25%,方法回收率98.05%~101.03%,日内RSD4.29%~9.83%,日间RSD5.21%~10.57%。结论:该法准确可靠,可用于头孢吡肟的临床药动学研究及临床特殊人群的血药浓度测定。     

HPLC法测定头孢他啶在人椎间盘髓核的分布

目的建立头孢他啶血清、髓核浓度的测定方法,观察其对人体椎间盘的渗透性。方法15例腰椎间盘突出的患者,给予头孢他啶2 g,iv gtt,30 min。给药完毕后,即行手术取髓核,同时抽取静脉血,用HPLC法测定髓核和血清中头孢他啶浓度。结果头孢他啶为0.4~10 mg.L-1及25~300 mg.L-1时,药物浓度(ρ)X和药物峰面积与内标物峰面积之比(A头孢他啶/A内标)Y线性关系良好,血清标准曲线Y=4.905 1X 0.0092,r=0.9999;髓核标准曲线Y=4.564 0X 0.011 4,r=0.9996。头孢他啶在髓核中的药量分布个体差异较大,且髓核内药量与血清药物浓度间无相关性(P>0.05)。结论本法可同时测定头孢他啶在血清和髓核中的药物浓度,以满足临床药物监测的需要。     

Continuous versus intermittent infusion of cefepime in neurosurgical patients with post-operative intracranial infections

Cefepime is administered as an intermittent infusion (II); however, continuous infusion (CI) may be advantageous because β-lactam antibiotics exhibit time-dependent antibacterial activity. This retrospective, non-randomised, comparative study included 68 neurosurgical patients with post-operative intracranial infections treated with 4 g/day cefepime over 24 h as a CI (n = 34) or 2 g every 12 h as II (n = 34). CI controlled the intracranial infection more rapidly and effectively than II (6.6 ± 1.9 days vs. 7.8 ± 2.6 days; P = 0.036). By considering the minimum inhibitory concentrations (MICs) to be 4 μg/mL and 8 μg/mL, the percentage of time when the cefepime plasma or CSF concentrations were higher than the MIC (%T_>MIC) was calculated for each patient. For plasma cefepime concentrations, the %T_>MIC in the CI group was higher than in the II group (for MICs of 8 μg/mL, 100% vs. 75%, respectively). The mean calculated area under the curve (AUC) in the CI group was similar to the II group (1197.99 ± 72.15 μg h/mL vs. 890.84 ± 140.78 μg h/mL; P = 0.655). For CSF cefepime concentrations, the %T_>MIC in the CI group was higher than in the II group (for MICs of 4 μg/mL and 8 μg/mL, 83.3% and 75% vs. 25% and 0%, respectively). The mean calculated AUC for the CI group was higher than the II group (220.56 ± 13.59 μg h/mL vs. 86.34 ± 5.69 μg h/mL; P = 0.003). Therefore, CI of cefepime significantly enhanced the antibacterial effect and reduced the treatment duration in neurosurgical patients with post-operative intracranial infections.