顺铂明胶微球的研制及相关生物学特性

目的 研制包裹有顺铂的颗粒型可降解性栓塞剂。方法 采用改良的双相乳化冷凝聚合法制备顺铂明胶微球，以原子吸收光谱分析为基础，测定顺铂明胶微球的包裹率、载药率及体外释药特性。结果 顺铂明胶微球颗粒直径均匀，药物包裹率91％。载药率17.4%，体外4b内缓释96％。结论 本法制得的顺铂明胶微球性质稳定，微球降解速率及药物释放速度基本符合临床要求。     

石墨炉原子吸收法测定血浆顺铂含量

目的建立测定血浆中顺铂含量的方法。方法将血浆在1 000 r·min 1离心10 min后，取上清液，采用石墨炉原子吸收分光光度法测定顺铂的含量。结果人血浆中顺铂的回收率为94.7%～103.70%。结论该方法为一种可信度较高、操作性较强的血浆顺铂的测定方法。     

大鼠静注双环铂、卡铂与顺铂后铂的肾排泄与肾分布比较研究

目的比较顺铂、卡铂和双环铂3种铂制剂的肾排泄速度和肾组织中浓度,探讨铂类抗癌药的肾毒性机制,为临床用药提供参考。方法大鼠按铂元素10mg·kg-1剂量静脉注射3种铂制剂后,采用原子吸收法测定大鼠尿液中3种铂的排泄量,计算4h尿药累积排泄百分率。结果顺铂组4h的累积排泄量平均为(33.7±5.7)%;卡铂组为(89.1±8.5)%;双环铂组为(70.1±9.8)%,由此结果可见顺铂排泄最少,双环铂和卡铂则较多;静注顺铂、卡铂和双环铂后4h测定肾组织中铂的浓度分别为(70.6±31.6),(217.7±97.6)和(278.8±112.0)μg·g-1。结论与顺铂相比,双环铂与卡铂肾排泄较快,肾组织中的铂浓度相对较高,肾组织中铂浓度与肾毒性间可能无直接关系。     

涂覆处理石墨管、原子吸收法测定骨肿瘤患者血清和组织中微量铂

目的　开发一种涂覆石墨管测定肿瘤患者血清及组织中顺铂的方法。方法　采用石墨炉原子吸收光谱法。结果　钨涂覆石墨管能消除样品中基体干扰,给出较高的灵敏度和准确度。结论　涂覆石墨炉法快速、简单、准确,适用于血清和组织中顺铂的测定     

γ-聚谷氨酸-柠檬酸-顺铂复合物中顺铂含量测定方法的建立

目的建立γ-聚谷氨酸-柠檬酸-顺铂复合物中顺铂含量测定的方法。方法采用高效液相色谱法测定γ-聚谷氨酸-柠檬酸-顺铂复合物中顺铂含量,色谱柱为C18柱(4.6 mm×300 mm,5μm),流动相为含150mmol·L-1氯化钠的磷酸盐缓冲溶液(pH 7.4),流速为0.65 mL·min-1,检测波长为210 nm。结果顺铂质量浓度在4²00μg·mL-1范围内,其色谱峰面积与质量浓度的线性关系良好(r=0.999 7)。顺铂含量测定的加样回收率平均值为99.78%,RSD小于2%。测得γ-聚谷氨酸-柠檬酸-顺铂复合物中顺铂含量约为26%200μg·mL-1范围内,其色谱峰面积与质量浓度的线性关系良好(r=0.999 7)。顺铂含量测定的加样回收率平均值为99.78%,RSD小于2%。测得γ-聚谷氨酸-柠檬酸-顺铂复合物中顺铂含量约为26%²8%。结论该法灵敏度高、专属性强、可用于γ-聚谷氨酸-柠檬酸-顺铂复合物中顺铂的含量测定。     

改良高效液相色谱法测定血浆中顺铂磁性纳米药物的含量

目的建立高效液相色谱技术测定血浆中顺铂浓度的方法来进行药物代谢动力学的研究。方法用Waters色谱系统。色谱条件:2487双通道紫外检测器。C18色谱柱(大连依利特ODS2分析柱,250mm×4.6mm,5μm),外接菲罗门C18(4mm×4 mm保护柱)。恒温35℃,流速1.0ml·min-1,流动相水-甲醇(28∶72),Waters 1525泵,717自动取样器,进样量为20μl,Breeze色谱工作站。血浆中的顺铂经二乙基二硫代氨基甲酸钠衍生化后,用氯仿提取其产物Pt(DDTC)2,离心后直接取氯仿层进样,采用高效液相色谱仪在254 nm处测定药物浓度。结果本法能有效地测定兔血浆中的顺铂浓度。样品各组分分离良好,顺铂线性范围为0.20768-12.468 mg.L-1,相关系数r=0.9999,日间和日内变异系数均小于10%。结论该方法是一种高效、准确的检测方法,适用于顺铂药物动力学的研究。     

顺铂-可降解淀粉微球家兔动脉栓塞药动学研究

本实验利用顺铂－可解淀粉微球栓塞家兔胃动脉后,用原子吸收人姚光度计测定其血药浓度,胃、肾组织中顺铂的浓度,并作了体内药动学研究,最小检 为5ng/ml回收率为92．5％－103．7％,发现其药动学参数变化较小,但局部药物浓度明显提高,说明可降解淀粉微球携带化疗药物（顺铂）进行治疗时可以使化疗药物抗癌作用增强,肾毒性降低。     

顺氯氨铂的高效液相色谱法

HPLC法可能对顺氯氨铂(Cisplatin,简称顺铂)的功能团提供良好专属性,但由于顺铂在非水介质中溶解度差、UV 吸收低等原因,使许多较为方便的色谱法均不能采用。用溶剂发生阴离子交换剂HPLC 测定顺铂,勿论在峰形、柱效及稳定性方面均有明显优点。     

顺铂软膏制备及质量控制

目的 :研制顺铂软膏 ,建立测定顺铂含量的方法。方法 :采用顺铂衍生物经萃取后紫外分光光度法进行含量测定。软膏中顺铂用二乙基硫代氨基甲酸钠 (DDTC)衍生化 ,其产物溶于氯仿在 34 7.5nm波长处可进行测定。结果 :顺铂溶液 4～ 16 μg·ml-1范围内浓度与吸收度有良好线性关系 ,其回归方程为C =14.7377A - 0 .2 486 (r =0 .9992 ) ,平均回收率 (n =10 )为 80 .88% ,RSD =1.0 5 %。结论 :顺铂软膏性质稳定 ,应用紫外分光光度法测定软膏中顺铂含量快捷准确 ,简便易行     

顺氯氨铂临床分析进展

顺氯氨铂(简称顺铂)在水溶液中易发生亲核取代反应,但其在体内的生物转化产物至今尚未分离。临床样品中,顺铂的测定方法有紫外分光光度法(UV),无火焰原子吸收分光光度法(FAAS),X-射线萤光分析及高效液相层析法(HPLC)。前三种方法缺乏专一性,仅能测定铂的总浓度。其中,FAAS 法检测限为25     

进展期胃癌术前顺铂腹腔内、静脉化疗药代动力学的比较研究

目的：比较研究进展期胃癌术前顺铂静脉与腹腔内给药的药代动力学特点。方法：50例可切除进展期胃癌患者随机分成两组：腹腔给药组26例,静脉给药组24例。顺铂60mg／m2分别于术前腹腔及静脉给药,给药后180min,取腹腔液、胃左静脉血、外周血标本;270min取手术中肿瘤组织、癌旁正常组织标本。另取8例分两组分别作顺铂腹腔内给药与静脉给药的药代动力学研究。测定各组织的铂含量作为顺铂的浓度指标,铂浓度采用石墨炉原子分光光谱分析法测定。结果：顺铂腹腔给药时,在腹腔内可维持较长时间的高浓度,而血浆内的药物浓度与静脉给药时相近;腹腔给药时AUC为静脉给药时的近5倍;顺铂术前给药后,腹腔给药组腹腔液、胃左静脉的总铂浓度明显高于静脉给药组（P〈0．01）,分别高于静脉给药组的23．4倍、2．53倍;肿瘤组织内的浓度也比静脉给药组高,差异有统计学意义（P〈0．05）。结论：顺铂腹腔内给药具有明显的药代动力学优势,可作为进展期胃癌有效的辅助治疗手段。     

顺铂植入剂兔舌内植入药动学研究

目的 研究顺铂植入剂在兔舌内植入的药动学.方法 兔12只随机均分实验组、对照组,实验组舌内植入顺铂植入剂,对照组静注顺铂,用原子吸收法测不同时间血浆中顺铂浓度,求算药动学参数并比较.结果 实验组达峰时、峰浓度、清除率、平均驻留时间和AUC分别是对照组的650、0.06、0.32、4.45和2.07倍.结论 顺铂植入剂兔舌内植入作用时间长、舌内作用强度大、全身作用强度微小、药物利用率高,有利于舌癌治疗.     

缓释型顺铂瘤内治疗大鼠C6胶质瘤的药代动力学

目的　观察C6胶质瘤大鼠瘤内给予顺铂缓释剂 ,ip顺铂后 ,顺铂在瘤内、脑组织、血及肾中的分布。方法　瘤内给予 1mg·m- 2 顺铂缓释剂 ,ip 5 0mg·m- 2顺铂后 ,然后在不同时间取样 ,用原子吸收分光光度法测量顺铂含量。结果　瘤内顺铂浓度瘤内用药比全身用药平均高 2～ 5 0倍 ,血及肾中的顺铂浓度瘤内用药仅为全身用药的 1.6 %～ 10 %和 0 .4 5 %～ 14 %。结论　瘤内用顺铂缓释剂可明显提高局部药物浓度 ,降低血 ,肾中顺铂分布 ,减轻全身毒副作用 ,从而增强化疗效果     

In-vivo Microdialysis Study of the Distribution of Cisplatin into Brain Tumour Tissue after Intracarotid Infusion in Rats With 9L Malignant Glioma

Simultaneous brain microdialysis in tumour and non-tumour tissues has been used for kinetic determination of the local distribution of an anticancer agent, cisplatin, in rats. Rat brain was implanted with 9L malignant glioma and cisplatin (3.5 mg kg^?) was administered as a selective intracarotid infusion for 30 min to rats prepared for brain microdialysis. The amount of platinum in the dialysate collected from tumour and non-tumour brain tissues was determined by atomic absorption spectrophotometry, as representative of cisplatin. Total and free platinum concentrations in plasma were also measured. Free platinum is accumulated preferentially in the tumour tissue and the brain tumour distribution coefficient (the ratio of brain tumour platinum AUC to plasma free platinum AUC, where AUC is the area under the platinum concentration-time curve) was 0.69, although there was little distribution into normal brain tissue. Drug binding to plasma proteins was 65%. It is concluded that simultaneous microdialysis is an easy and available method for assessing in-vivo local pharmacokinetics and distribution of cisplatin in tumour and non-tumour tissues of the brain.     

Pharmacokinetics of cisplatin administered by continuous hyperthermic peritoneal perfusion (CHPP) to patients with peritoneal carcinomatosis

The pharmacokinetics of cisplatin administered by continuous hyperthermic peritoneal perfusion (CHPP) was characterized in patients with peritoneal carcinomatosis. Cisplatin was added into the perfusate with escalating doses from 100 mg/m2 to 400 mg/m2. The hyperthermic perfusion was maintained for 90 minutes with a flow rate of 1.5 L/min and a target peritoneal temperature of 42.5 degrees C after a tumor debulking procedure. Samples of both the perfusate and blood were obtained during the perfusion and 30 minutes after the perfusion. Cisplatin plasma and perfusate concentrations were determined by flameless atomic absorption spectrometry with a lower limit of detection of 2 ng/ml and a coefficient of variation (CV) < 10%. Fifty-six patients were enrolled in the study. The mean (+/- SD) percentage of cisplatin present in the perfusate at the completion of perfusion was 27.8% +/- 20% of the total dose. The maximum cisplatin concentrations in the perfusate were 10 times higher than those in plasma. The area under the concentration-time curve (AUC) of the perfusate was 13 times higher than the AUC of plasma. A two-compartment model with an additional peritoneal cavity compartment fits to the data best based on the Akaike information criterion. However, the interpatient variability was considerably high (CV < 100%). In conclusion, cisplatin administered by hyperthermic peritoneal perfusion resulted in a pharmacological advantage by obtaining higher and direct drug exposure to the tumor in the peritoneal cavity while limiting systemic absorption and toxicity. Using a complex two-compartment model, the authors were able to characterize the pharmacokinetics of cisplatin given intraperitoneally via this technique.     

Local distribution into brain tumor and pharmacokinetics of 4-pyridoxate diammine hydroxy platinum, a novel cisplatin derivative, after intracarotid administration in rats with 9L malignant glioma: simultaneous brain microdialysis study

Local distribution into brain tumor and the pharmacokinetics of 4-pyridoxate diammine hydroxy platinum (PyPt), a novel cisplatin derivative, were examined using rats implanted with 9L glioma and compared with cisplatin. PyPt (5.0 mg/kg) and cisplatin (3.5 mg/kg) were administered as selective intracarotid infusions for 30 min to the rats. Dialysates from extracellular fluid (ECF) in tumor and non-tumor brain tissues were collected by simultaneous microdialysis. The amount of platinum was determined by atomic absorption spectrophotometry, as representative of the drug administered. Plasma concentration of total and protein unbound platinum, and urinary excretion amount and tissue distribution of total platinum were also determined. Unbound platinum was accumulated preferentially in the brain tumor tissue ECF after drug administration, while there was little distribution into normal tissue ECF of the brain. In the brain tumor, the values of the unbound platinum AUC and MRT, where AUC is the area under the concentration-time curve and MRT is the mean residence time, for PyPt were 1.7 and 1.3 times larger than with cisplatin, respectively. The brain tumor distribution coefficient (the ratio of brain tumor ECF platinum AUC to plasma protein unbound platinum AUC) for PyPt (0.85) was higher than that for cisplatin (0.69), indicating that the local amount of platinum distributed into the glioma is enhanced by PyPt rather than by cisplatin. The binding to plasma proteins of PyPt (23%) was lower than that of cisplatin (65%). The total platinum concentration in tissues after administration of PyPt was significantly lower than that of cisplatin in the kidney, liver and spleen. In addition, the urinary excretion amount of total platinum after the administration of PyPt was significantly larger than that of cisplatin. These results suggested that PyPt is easily eliminated by rapid urinary excretion because of its reduced interaction with plasma proteins and poor distribution to the kidney or reticuloendothelial tissues such as the liver and spleen. It is concluded that PyPt is an effective cisplatin derivative for the treatment of gliomas with the added advantage of enhancing local distribution of drug into the brain tumor and reducing its accumulation in the kidney, which has previously caused severe nephrotoxicity.     

顺铂植入剂植入给药的体内外相关性

 目的：探索顺铂植入剂的体内外相关性指标。方法：体内试验采用肿瘤局部植入给药,原子吸收光谱法测定血药浓度,建立药动学模型并计算体内吸收率;体外采用改良的大杯法测定体外释放度,取样时间点为预选的关联时间点;体内外相关按中华人民共和国药典规定的“点对点”方法进行。结果：体内药动学模型为一室缓释模型,体外释放为一级方程,体内外相关试验的对应时间点数n=10,统计自由度ν=9,体内外相关系数r=0.884 2,大于临界相关系数0.847 0（P=0.001）。结论：提示本试验的体内吸收和体外释放过程具有较好的相关性。     

Pharmacokinetic advantage of intra-arterial hepatic oxaliplatin administration: comparative results with cisplatin using a rabbit VX2 tumor model

The aim of this study was to compare intra-arterial hepatic administration (IAH) versus i.v. administration of oxaliplatin and cisplatin in a VX2 tumor model in rabbits. VX2 tumors were implanted in the livers of White New Zealand female rabbits and 2 weeks later they received either cisplatin (4 mg/kg) or oxaliplatin (6 mg/kg) administered by IAH or i.v. Platinum pharmacokinetic parameters were measured by atomic absorption spectrometry at baseline, 2, 5 10, 20, 40 and 60 min, and then at 2, 4, 6 and 24 h after drug administration. Animals were sacrificed 24 h after drug administration to measure platinum concentrations in various tissues. After IAH oxaliplatin administration, we observed a significant decrease for total and filterable platinum in the Cmax compared with i.v. administration (12.4 versus 18.2 microg/l; p=0.02 and 11.2 versus 17.3 microg/l; p=0.02, respectively). Significant differences in various tissue concentrations were reported when comparing IAH and i.v. administration of oxaliplatin with IAH administration offering an advantage over i.v. administration. No differences in pharmacokinetic parameters or platinum tissue accumulation were apparent between the IAH and i.v. administration with cisplatin. We conclude that there is a significant pharmacokinetic advantage to using oxaliplatin for locoregional IAH chemotherapy compared with i.v. administration.     

微波消解-石墨炉原子吸收分光光度法测定药用明胶空心胶囊中铬的含量

目的建立微波消解-石墨炉原子吸收分光光度法测定药用空心胶囊中有害元素铬的含量。方法采用微波消解压力控制系统消解样品,以石墨炉原子吸收分光光度法检测药用空心胶囊中铬元素的含量。结果方法的检出限为0．16μg·L^-1,铬浓度在0～20μg·L^-1范围内与吸光度呈良好的线性关系（r=0．9997）,平均回收率为101．9％。结论该方法不用加基质改进剂,操作简便、快捷,可满足地市级药检所对药用空心胶囊中微量铬含量的测定。