RP—HPLC法测定替米沙坦含量及有关物质

目的:采用反相高效液相色谱法测定替米沙坦的含量及有关物质。方法:色谱柱为Alltech公司Alltima C_(18)柱(150 mm×4.6 mm,5 μm),以乙腈-0.01 mol·L~(-1)醋酸铵缓冲液(60:40,用醋酸调节pH=6.0)为流动相,流速1.0 mL·min~(-1),检测波长分别为298 nm(含量测定)与255 nm(有关物质测定)。结果:替米沙坦在50-250μg·mL~(-1)范围内呈良好的线性关系,r=0.9999;最低检出限0.04 ng;日内精密度(RSD<0.5%)与日间精密度(RSD<0.5%)良好。结论:本方法简便、快速,结果准确、可靠。     

高效液相色谱法及紫外分光光度法测定替加色罗片的含量

目的 :建立替加色罗片剂含量测定的HPLC法和UV法。方法 :HPLC法———采用C18柱 ,流动相为乙腈∶1%十二烷基硫酸钠缓冲溶液 (含0 .95 %冰醋酸 ) =5 6∶4 4。流速 :2mL·min- 1。检测波长 :314nm。柱温 :4 0℃。UV法———在 314nm处测定替加色罗的吸收度。结果 :HPLC法在 0 .1～ 12 0mg·L- 1的范围内 ,将峰面积A与浓度C进行回归处理 ,A =2 8.93C - 14 .4 6 (r =0 .9999,n =6 ) ,日内RSD≤ 1.11% ,日间RSD≤ 3.0 9% ,回收率在 10 0 .4 2 %～ 10 3.82 %之间。UV法在 2～ 2 0mg·L- 1范围内线性良好 ,回归方程为A =5 4.2 8C +0 .0 14 8(r =0 .9998,n =7) ,日内RSD≤ 0 .70 % ,日间RSD≤ 0 .92 % ,回收率在 10 1.0 6 %～ 10 3.0 2 %之间。 2种方法测得 3批样品的标示量百分含量均在规定范围内 (90 %～ 110 % )。结论 :HPLC法和UV法均适用于替加色罗片剂的含量测定 ,由于UV法更简便易行 ,在对有关物质进行了较好控制的情况下 ,此法更为适用     

RP-HPLC法测定硝唑尼特含量及有关物质的方法学研究

目的:反相高效液相色谱法测定硝唑尼特的含量及其有关物质。方法:C18色谱柱(4.6 mm×150mm,填料:Hypersil,粒度:5μm),以乙腈-10 mmol·L-1甲酸(60:40)为流动相,流速0.8 mL·min-1,波长240 nm测定。结果:反相高效液相色谱法测定的线性范围为20.0-120.0μg·mL-1,相关系数为0.9998;最低检测限1.0 ng;样品溶液至少在24 h内稳定(RSD<1.0％);进样精密度(RSD<0.1％)良好。结论:本法简便、快速、准确,可用于硝唑尼特含量及其有关物质的测定。     

HPLC测定恩替卡韦中的有关物质

目的 采用HPLC法测定恩替卡韦中的有关物质.方法 采用ODS-AQ C18色谱柱(250 mm × 4.6 mm,5μm),流动相A为乙腈-水(3∶97),流动相B为乙腈,梯度洗脱,流速1.0 mL·min-1,检测波长254 nm,柱温35℃.结果 恩替卡韦与降解杂质能完全分离,分离度为2.99;检测限和定量限分别为20、68 ng·mL-1,精密度良好(RSD=0.73％).结论 所用方法灵敏、准确、操作简便、专属性强,可用于测定恩替卡韦原料药及片剂中的有关物质.     

高效液相色谱法测定马来酸替加色罗缓释微丸胶囊中主药的含量

目的建立以高效液相色谱法测定马来酸替加色罗缓释微丸胶囊中马来酸替加色罗含量的方法。方法以Kromasil C18(250.0mm×4.6mm,5μm)为色谱柱,流动相为乙腈-0.2%磷酸溶液=40:60,检测波长为315nm,流速为1ml/min,柱温为30℃,进样量是20μl。结果马来酸替加色罗在32.8～328.4μg/ml范围内进样量与峰面积呈良好的线性关系(r=0.9997),平均回收率为99.91%,RSD=0.9%。结论本方法简便、准确、专属性强,可用于该制剂的含量测定。     

HPLC法测定硝呋拉呔的含量及有关物质的方法学研究

目的:采用高效液相色谱法测定硝呋拉呔的含量及有关物质。方法:采用ODSC_(18)色谱柱(5μm,4.6mm×250mm),以甲醇-水(45:55)为流动相,流速1.2 mL·min~(-1),紫外检测器于254 nm测定。结果:HPLC法测定的线性范围为0.01～0.4mg·mL~(-1),r=0.999 9,最低检测限0.2 ng;样品溶液在8 h内稳定,日内精密度和日间精密度(RSD<1.0％)良好。回收率为100.1％。结论:采用HPLC法测定硝呋拉呔及有关物质的方法简便,结果可靠。     

HPLC法测定马来酸氨氯地平分散片中主药及有关物质含量

目的:建立以高效液相色谱法测定马来酸氨氯地平分散片中主药及有关物质含量的方法。方法:采用LichrospherC18为色谱柱,以甲醇-0.03mo·lL-1磷酸二氢钾(70∶30)为流动相,检测波长为237nm,流速为1mL·min-1,柱温为30℃。结果:马来酸氨氯地平检测浓度线性范围为31.94～127.75μg·mL-1(r=0.9998,n=5),平均回收率为99.5%(RSD=0.39%,n=9);样品中有关物质含量均小于0.38%。结论:该方法简便、快速、准确、专属性好,适于马来酸氨氯地平分散片的质量控制。     

RP-HPLC法测定盐酸拓扑替康及制剂含量和有关物质

目的:建立高效液相色谱法测定盐酸拓扑替康(TPT)及制剂中有关物质和含量。方法:采用十八烷基硅烷键合硅胶为填充剂,0．5％磷酸和0．5％正丁胺(v／v)溶液-甲醇(60:40)为流动相,流速1．0 mL·min-1,检测波长为267 nm。结果:盐酸拓扑替康与有关物质分离良好,线性范围为10-100μg·mL-1(r=0．9999),最低检出量为0．02 ng。方法精密度(RSD)为 0．41％(n=9)。制剂平均回收率为99．3％。结论:方法快速简便,准确,可用于原料及制剂中有关物质和含量的测定。     

HPLC测定盐酸莫西沙星的含量和有关物质

目的 采用HPLC法测定盐酸莫西沙星的含量及其有关物质.方法 采用Hypersil ODS2色谱柱(250 mm×4.6 mm,5μm),以10％四丁基氢氧化铵水溶液、硫酸和磷酸二氢钾的混合溶液-甲醇-乙腈为流动相,梯度洗脱,检测波长296 nm,流速1.0 mL· min-.结果 1 ～ 200 μg· mL-盐酸莫西沙星与峰面积的线性关系良好(r=0.9999),精密度试验的RSD=0.6％,重复性试验的RSD =0.6％ (n =6);平均回收率为99.4％,RSD =0.5％ (n =9).结论 所用方法具有良好的稳定性、精密度及重复性,适用于测定盐酸莫西沙星的含量及其有关物质.     

HPLC法测定盐酸纳美芬的含量及其有关物质

目的:建立高效液相色谱法测定新药盐酸纳美芬及其注射剂的含量及其有关物质。方法:采用迪马公司C18钻石色谱柱(250 mm×4．6 mm,5μm);流动相:乙腈-0．05 mol·L-1的磷酸缓冲液(20:80),其中1 000 mL缓冲液中含有7．8 g磷酸二氢钠和2 mL的三乙胺,用85％的磷酸调节pH为4．2±0．02;流速:1．0 mL·min-1;检测波长为210 nm。结果:HPLC法测定的线性范围为21-126μg·mL-1,r=1．000,最低检测限为0．2 ng,本方法的重复性和精密度良好(RSD<2％),平均回收率为99．30％-99．42％。结论:采用HPLC法测定盐酸纳美芬及其注射液的含量和有关物质,方法简便,结果准确。     

成骨细胞的功能与损伤和骨质疏松的防治

骨质疏松是一种全身性骨骼疾病,导致骨折风险增加。成人的骨量通过破骨细胞的骨吸收和成骨细胞的骨形成作用来维持动态平衡,治疗骨质疏松症的理想策略是抑制破骨细胞的骨吸收和/或增强成骨细胞的骨形成功能。目前针对保护成骨细胞及增强其功能的骨质疏松疗法相对较少。因此,本文针对成骨细胞相关功能蛋白、各种细胞损伤机制（内质网应激、氧化应激、机械过载、微小RNA和长链非编码RNA的影响等）及骨质疏松的治疗与预防作一综述,以期为针对增强成骨细胞功能的骨质疏松治疗策略提供新思路。     

Comparison of formation of thiolactones and active metabolites of prasugrel and clopidogrel in rats and dogs

1. Prasugrel and clopidogrel are antiplatelet prodrugs that are converted to their respective active metabolites through thiolactone intermediates. Prasugrel is rapidly hydrolysed by esterases to its thiolactone intermediate, while clopidogrel is oxidized by cytochrome P450 (CYP) isoforms to its thiolactone. The conversion of both thiolactones to the active metabolites is CYP mediated. This study compared the efficiency, in vivo, of the formation of prasugrel and clopidogrel thiolactones and their active metabolites.

2. The areas under the plasma concentration versus time curve (AUC) of the thiolactone intermediates in the portal vein plasma after an oral dose of prasugrel (1 mg kg^?1) and clopidogrel (0.77 mg kg^?1) were 15.8 ± 15.9 ng h ml^?1 and 0.113 ± 0.226 ng h ml^?1, respectively, in rats, and 454 ± 104 ng h ml^?1 and 23.3 ± 4.3 ng h ml^?1, respectively, in dogs, indicating efficient hydrolysis of prasugrel and little metabolism of clopidogrel to their thiolactones in the intestine.

3. The relative bioavailability of the active metabolites of prasugrel and clopidogrel calculated by the ratio of active metabolite AUC (prodrug oral administration/active metabolite intravenous administration) were 25% and 7%, respectively, in rats, and 25% and 10%, respectively, in dogs.

4. Single intraduodenal administration of prasugrel showed complete conversion of prasugrel, resulting in high concentrations of the thiolactone and active metabolite of prasugrel in rat portal vein plasma, which demonstrates that these products are generated in the intestine during the absorption process.

5. In conclusion, the extent of in vivo formation of the thiolactone and the active metabolite of prasugrel was greater than for clopidogrel’s thiolactone and active metabolite.

     

PTEN和DNA含量与非小细胞肺癌侵袭转移的关系探讨

目的 研究非小细胞肺癌(NSCLC)组织中抑癌基因PTEN的表达和DNA含量与NSCLC侵袭、转移的关系.方法 采用免疫组织化学SP方法检测PTEN在78例肺癌标本中的表达,并用流式细胞术检测30例肺癌标本中DNA含量.结果:肺癌标本中PTEN蛋白总缺失率为42.3%,有淋巴结转移组和无淋巴结转移组肺癌表达缺失率分别为52.1%和26.7%(P＜0.05),其表达缺失率随TNM分期增加而上升,分期越晚表达缺失率越高.PTEN缺失率高者生存时间短.DNA指数(DI)的分布范围在1.04～1.93.异倍体肿瘤24例,DI值随TNM分期增加而增加(P＜0.05),与淋巴结转移呈正相关.结论 肺癌组织中PTEN的表达与肺癌淋巴结转移有显著相关性,肺癌细胞DNA含量与肺癌TNM分期及淋巴结转移密切相关.检测PTEN蛋白表达和DNA含量将有助于判断肺癌的转移及预后.     

阿立哌唑与利培酮治疗自闭症谱系障碍与注意缺陷多动障碍共病患儿的疗效与安全性评价

目的：评价阿立哌唑与利培酮治疗自闭症谱系障碍（ASD）与注意缺陷多动障碍（ADHD）共病患儿的疗效与安全性。方法：选取在某院精神科治疗的ASD和ADHD共病患儿68例,根据随机数字表法将患儿分为阿立哌唑组（n=34）和利培酮组（n=34）。阿立哌唑组患儿接受起始剂量为5 mg·d^-1的阿立哌唑片口服治疗,最终剂量增加至15 mg·d^-1。利培酮组患儿接受起始剂量为1 mg·d^-1的利培酮片口服治疗,最终剂量增加至2 mg·d^-1;2组患儿均治疗12周。在基线（T₀）、治疗6周（T₁）与12周（T₂）时,采用注意缺陷/多动评定量表（ADHD-RS）评价患儿总体ADHD症状变化情况;采用康纳斯行为评定量表（CRSR）教师用量表多动因子（CRSR-I）评价患儿多动症的改善情况;采用CRSR不注意缺陷-冲动因子（CRSR-H）评价患儿注意力缺陷的改善情况;采用临床整体印象-严重程度量表（CGI-S）及儿童总体评估量表（C-GAS）评分评价患儿整体功能。对患儿的相关临床指标进行常规监测,比较2组患儿药物不良事件与安全性。结果：与T₀时比较,阿立哌唑组患儿T₁与T₂时,ADHD-RS、CRSR-I、CRSR-H与CGI-S评分均显著降低（均P<0.05）,C-GAS评分显著提高（P<0.05）。利培酮组患儿T₂时,ADHD-RS、CRSR-I、CRSR-H与CGI-S评分均显著降低（均P<0.05）,C-GAS评分显著提高（P<0.05）。2组患儿的ADHD症状显著改善,多动症状与不注意缺陷-冲动症状显著改善,患儿的整体功能也显著改善。2组患儿主要的不良事件是食欲增加、体质量增加与嗜睡,但均没有发生严重的不良事件。T₂时,利培酮组患儿催乳素水平显著提高（t=9.619,P<0.001）,其他临床指标没有显著性差异（均P>0.05）。结论：阿立哌唑和利培酮能够通过减少ASD和ADHD共病患儿的注意力涣散和多动症症状来改善患儿整体功能,具有较高的疗效、安全性,值得临床推广应用。     

阿立哌唑与利培酮治疗痴呆精神行为症状的疗效及安全性比较

目的观察阿立哌唑和利培酮治疗老年痴呆精神行为症状的疗效及安全性。方法采用随机对照研究,将具有精神行为症状的痴呆患者68例完全随机分为阿立哌唑组及利培酮组,各34例。阿立哌唑组患者服用阿立哌唑,起始剂量2．5mg／d,最大剂量不超过15mg／d;利培酮组患者口服利培酮,起始剂量0．5mg／d,最大剂量不超过3mg／d。疗程均为8周。治疗前和治疗第2、4、8周末采用痴呆病理分析评定量表（BEHAVE—AD）评定疗效,用副反应量表（TESS）评定不良反应,并于入组时和治疗第8周末分别检测2组患者空腹血糖、餐后2h血糖、TC、TG、LDL—C、HDL—C及体重。结果阿立哌唑组和利培酮组患者治疗2、4、8周后BEHAVE—AD评分均明显低于治疗前[阿立哌唑组：（14．8±4．2）、（10．2±3．6）、（6．8±2．8）分比（16．4±4．6）分;利培酮组：（15．2±3．9）、（11．8±3．8）、（7．2±3．0）分比（17．2±5．O）分,P〈0．05或P〈0．01]。2组患者间治疗前及治疗后BEHAVE—AD评分比较,差异均无统计学意义（P〉0．05）。2组不良反应发生率均为8．8％（3／34）,差异无统计学意义（P〉0．05）。利培酮组治疗8周末体重较治疗前增加明显[（71±6）kg比（66±6）kg,P〈0．05],TG及LDL—C升高[分别为（1．62±0．46）mmol／L比（0．96±0．29）mmol／L．（3．82±0．86）mmol／L比（3．08±0．74）mmol／L,而阿立哌唑组则改变不明显（均P〉0．05）。结论阿立哌唑治疗老年痴呆精神行为症状总体疗效、安全性与利培酮相当,但阿立哌唑对患者血糖、血脂及体重影响小于利培酮。     

Correlation of behavioral and neurochemical effects of d- and l-amphetamines

In an attempt to correlate the behavioral and neurochemical effects of d- and l-amphetamines, the time courses of the effects of the two isomers (1 mg/kg; base, i.p.) were studied on spontaneous motor activity (SMA) and stereotyped behavior (ST) as well as on the concentrations of norepinephrine (NE), dopamine (DA), and serotonin (5-HT) in discrete brain areas, such as the caudate nucleus (CN), pons-medulla (PM), and diencephalonmidbrain (DM) in rats. In addition, the dose-response relationship for d-isomer (0.5–2 mg/kg, i.p.) and l-isomer (1–4 mg/kg, i.p.) was also studied on SMA and ST. SMA increased with the dose up to 1.5 mg/kg for d-isomer and up to 3 mg/kg for l-isomer and then decreased, whereas ST increased with the dose for both the isomers. At 1 mg/kg dose, SMA reached its peak during the fourth postdrug 20–minute period for both d- and l-isomers, whereas ST reached its peak during third to fifth 20-minute periods for d-isomer and during the third period for the l-isomer. The d-isomer significantly increased the DA levels in the CN and DM at 30 minutes postdrug, which reached their maximum at 60 minutes, whereas NE levels in the PM had no significant change at 30 minutes, but were significantly reduced in the DM at 30 minutes and in both PM and DM at 60 minutes postdrug; 5-HT levels in the PM and DM showed no significant change. Compared to d-amphetamine, the l-isomer at 30 and 60 minutes postdrug caused more or less similar changes in the NE levels in the DM and PM, whereas it produced less increase in the DA levels in the CN and DM and significant decrease in 5-HT levels in the DM and PM. It appears that the difference in the behavioral effects induced by the two isomers of amphetamine may be due to the difference in their effects on dopaminergic and serotonergic systems.     

Quantification and prediction of skin pharmacokinetics of amoxicillin and cefuroxime

The purpose of this project was to develop and validate a pharmacokinetic model and to quantify the rate and extent of distribution between plasma and skin of two β‐lactam antibiotics, amoxicillin (AMX) and cefuroxime (CFX), which are frequently administered systemically to treat skin and skin structure infections. Dosing regimens are usually based on plasma concentration, however, concentrations at the target site are better correlated with the effect. For each antibiotic, three different i.v. bolus doses were administered to three female rabbits according to a randomized cross‐over design and plasma samples were collected serially. Skin concentrations were obtained by continuous microdialysis. Skin and unbound plasma concentrations were fitted simultaneously using a semi‐physiological model and the transfer constants plasma/skin (K_in) and skin/plasma (K_out) were estimated. K_in and K_out were then used to predict skin concentrations from the plasma levels obtained from an oral administration of AMX or from an i.v. bolus of CFX. The predicted skin profiles were similar to those measured by microdialysis during the actual experiments. In conclusion, this study shows that it is possible to generate a reasonable prediction of skin pharmacokinetics from any plasma level once a careful characterization of the transfer process between plasma and skin has been made. Copyright © 2009 John Wiley & Sons, Ltd.     

乙肝两对半、前S1抗原与HBV-DNA含量的测定与比较

目的　探讨乙肝两对半、前 S1抗原与 HBV- DNA含量的关系。方法　 183 0份血清用 EL ISA方法测定 HBV“两对半”和前 S1抗原 ,用荧光定量 PCR方法检测 HBV- DNA含量。结果　不同两对半模式血清 HBV-DNA阳性率不同 ,检出率以 HBs Ag( )和 /或 HBe Ag( )组最高 ;共检出前 S1抗原阳性血清 73例 ,其中 HBV-DNA检出率为 90 .4% ( 66/ 73 )。结论　前 S1抗原与 HBe Ag、HBV- DNA有较好相关性 ;FQ- PCR检测可更准确反映 HBV感染及复制情况