New Method for Optimization and Simultaneous Determination of Sparfloxacin and Non Steroidal Anti-Inflammatory Drugs: Its <i>In-Vitro</i>Application

A simple reversed phase HPLC method was developed and validated for the simultaneous determination of sparfloxacin (SPFX), diclofenac sodium, meloxicam, ibuprofen, flurbiprofen, naproxen and mefenemic acid in a relatively short time with high linearity in bulk material, pharmaceutical formulations and human serum. Purospher STAR C18 (250 × 4.6 mm, 5 μm) column was utilized with mobile phase, methanol and water (90:10, v/v pH 2.70 adjusted by phosphoric acid), was delivered at a flow rate of 1.5 mL.min–1. Eluent was monitored using UV detector at 240 nm. The proposed method is specific, accurate (98.42% - 102.75%), precise (intra-day and inter-day variation 0.011% - 1.85%) and linear (R2 > 0.999) with in the desired range 0.15 - 40 μg.mL–1 and the detection and quantification limit was 1.19E+08 – 0.150 μg.mL–1 and 3.62E+08 – 0.4574 μg.mL–1 respectively for SPFX and NSAIDs. The analysis of variance (ANOVA) and student’s t-test were applied to verify the results. The anticipated method is applicable to routine analysis of SPFX and NSAIDs in pharmaceutical formulations as well as in human serum samples. It has also applied on interaction of SPFX with NSAIDs.

Simple and sensitive determination of sparfloxacin in pharmaceuticals and biological samples by immunoassay

Plasma quinolone concentrations are not routinely measured in clinical practice.However,in order to optimize quinolone treatment,monitoring of plasma concentrations could sometimes be useful particularly in critically ill patients.In this study,anti-sparfloxacin antibody was obtained by immunizing rabbits with sparfloxacin conjugated with bovine serum albumin using isobutyl chloroformate method.After the assay procedure was optimized,the standard curve of sparfloxacin was established.The practical measuring range of the competitive ELISA extended from 5 ng/mL to 2 mg/mL.The recovery rates and coefficients of variation for rat plasma,urine and tissues were 87.7-106.2% and 4.8-15.3%,respectively.To demonstrate the potential of the ELISA,a preliminary pharmacokinetics and tissue distribution study of sparfloxacin in rats and quantitative analysis of sparfloxacin in several pharmaceuticals were performed and compared with high-performance liquid chromatography(HPLC).The experimental data indicated that the proposed method would be a valuable tool in therapeutic drug monitoring(TDM) for sparfloxacin.

Determination of Sparfloxacin in Human Urine by Reversed-Phase High Performance Liquid Chromatography With Nitrous Acid and Hydroiodic Pre-Column Derivatization

Sparfloxacin can be oxidized by nitrous acid, then react with hydroiodic acid to form a fluorescent derivative. Based on this, a reversed-phase high performance liquid chromatographic pre-column derivatization new method is described for the determination of sparfloxacin in human urine. The linear range is 0.05 mg/L to 4.0 mg/L, the recoveries are 91.5%similar to 95.7% and the RSD is 1.2%similar to4.2%. The results showed that this method is suitable for the determination of sparfloxacin in human urine.

Study on Fluorescence Property of Sparfloxacin Derivatizing System and its Application

In acid medium, sparfloxacin is oxidized by nitrous acid, then reacts with hydrobromic acid to form a new fluorescence substance, which can emit the strong fluorescence. which is 151 fold more than that of sparfloxacin itself. By this, a new sensitive method for the determination of sparfloxacin in human urine by derivative-synchronous fluorescence is presented with good results.

Studies on Reaction Mechanism Between Sparfloxacin and Bovine Serum Albumin

The binding of sparfloxacin and bovine serum albumin(BSA) in aqueous solution was studied by means of fluorescence and absorbance spectra, and the interactions influenced by Fe 3+ and Cu 2+ were explored. Based on the Scatchard′s site binding model and fluorescence quenching, practical formulas for a small molecule ligand attaching to a bio-macromolecule are proposed. The binding parameters were measured according to the suggested models, and the binding distance, the transfer efficiency of energy between sparfloxacin and BSA were obtained in view of the Frster theory of non-radiation energy transfer. The effect of sparfloxacin on the conformation of BSA was analyzed by means of synchronous fluorescence spectroscopy.

新喹诺酮类合成抗菌剂Sparfloxacin

斯帕沙星(Sparfloxacin)为广谱的新喹诺酮类合成抗菌剂,对包括肺炎球菌、甲氧西林耐药性金黄色葡萄球菌的革兰阳性菌、包括绿脓杆菌、沙雷菌、包括葡萄糖非发酵菌的革兰阴性菌、厌氧菌、军团菌、支原体、衣原体、结核菌、非定型抗酸菌等均显示出广泛的抗菌活性,其抗菌效力在新喹诺酮类中属最强者。

Sparfloxacin和KRM-1648对裸鼠麻风的疗效

氟喹诺酮碳酸类新抗菌药Sparfloxacin(SPFX)和利福霉素衍化物KRM-1684,用于裸鼠实验性麻风时每周5天连续给药,其最小有效剂量分别为5～10毫克/公斤和0.6毫克/公斤。作者研究了每周1～2次间歇给药的疗效。以Thai 53株的麻风菌(第7代)制成1×10~7/0.05毫升(实验1)和3×10~7/0.05毫升(实验2)的生理盐水悬液分别接种于10只雌裸鼠,接种后第3～5个月中给SPFX每周2次,每次10毫克/公斤和20毫克/公斤。

Sparfloxacin对接种于裸鼠足垫的麻风分枝杆菌的抗菌活性

目前,大多数人相信用DDS,B663和RFP联合化疗治疗麻风病是可靠的。但是,麻风菌对这些药的每一种都有耐药的报道,DDS是抑制剂,B663有不利的副作用,即皮肤色素沉着。RFP是可靠的杀菌药物,但是价格太贵。因此,需要发展新的,与现有的抗麻风药无交叉耐药、有杀菌作用、毒性小和比RFP价格低的抗麻风药。

Determination of Sparfloxacin Concentrations in Chicken Serums and Residues in Chicken Tissues and Manures Using Self-Ordered Ring Fluorescence Microscopic Imaging Technique

Based on the self-ordered ring(SOR) fluorescence microscopic imaging technique on a hydrophobic glass slide with Zn 2+ and cetyltrimethyl ammonium bromide(CTMAB) as sensitizer,and poly(vinyl alcohol)-124(PVA-124) and NH 3-NH 4 Cl(pH 10.00) as the medium,a method has been developed for determining sparfloxacin(SPFX) concentrations in chicken serum and residues in chicken tissues and manures.When the droplet volume was 0.20 μ L,SPFX was determined in the range of 1.38×10-13 ～2.03×10-12 mol.ring-1(or 6.90×10-7 ～1.02×10-5 mol.L-1),and the limit of detection(LOD) was 14fmol.ring-1(or 6.90× 10-8 mol.L-1).The recoveries of SPFX at all different spiked levels are in the range of 90.74%～106.61% when the methanol or acetonitrile were used as extracting agent,respectively,and the relative standard deviations(RSDs) are less than 3.0%.This study expands the applied fields of SOR technique in drug concentrations and residues determination.

荧光法研究司帕沙星与白蛋白的作用

本文用荧光光谱法、分光光度法研究了水溶液中喹诺酮类药物司帕沙星与牛血清白蛋白 (BSA)、鸡蛋白 (CEA)的相互作用 ,求得它们间的结合常数为K鸡 =8 2 9× 10 6,K牛 =4 41× 10 7;结合位点数分别为n鸡=0 5 88,n牛 =0 793,并根据F rster非辐射能量转移机制 ,测定了司帕沙星与两种血清白蛋白相互结合时其给体 受体间距离 (R鸡 =1 99nm ,R牛 =2 0 9nm)和能量转移效率 (E鸡 =0 76 6 ,E牛 =0 714)。实验表明 ,随着温度升高 ,BSA及CEA的猝灭曲线斜率降低 ,证实了司帕沙星与BSA和CEA的相互结合作用为单一的静态猝灭过程 ,其作用机制属能量转移机制。通过两种血清白蛋白与抗菌药物司帕沙星结合反应 ,探讨了药物司帕沙星在生物体内与蛋白质的相互作用的生物学效应及其作用机理。

流动注射光化学敏化化学发光法测定斯帕沙星

斯帕沙星 (SPFX)在酸性介质中经紫外光照射发生光化学反应 ,其产物与Tb3+ 形成络合物 ,对Ce SO2 - 3化学发光体系有增敏作用。据此 ,采用流动注射技术 ,建立了光化学敏化化学发光测定SPFX的新方法。方法的检出限为 2 .5× 10 - 8mol/L ;SPFX浓度在 1.0× 10 - 7～ 1.0× 10 - 5mol/L范围内与发光强度呈良好的线性关系。对 6.0× 10 - 6 mol/LSPFX平行测定 11次 ,RSD为 3 .8%。利用该法测定了片剂和胶囊中SPFX的含量 。

国产司帕沙星片在老年人体内的药动学研究

目的 研究老年人po司帕沙星片的药动学特点。方法 用HPLC测定 8例老年人po 2 0 0mg司帕沙星片后 12 0h内血样和尿样中司帕沙星浓度 ,采用 3P87药动学程序对血药浓度 时间数据进行线性拟合 ,计算药动学参数。根据尿药浓度和尿量计算该药尿原型药物排泄率。结果 本实验建立的HPLC线性关系、回收率、日内及日间精密度均能满足药动学研究的要求 ,老年人 po司帕沙星片后血药浓度 时间数据符合二室模型 ,主要药动学参数为t1/ 2 β=(2 6 .11± 6 .4 9)h ,tmax=(2 .74±1.4 2 )h ,cmax=(1.15± 0 .14 )mg·L-1,AUC0～∞ =(37.2 9± 11.17)mg·h·L-1。服药后 12 0h平均尿原型药物排泄率为2 4 .14 %。结论 老年人半衰期达 2 6h ,单剂 po 2 0 0mg 4 8h后血药浓度均高于绝大多数细菌的MIC及MBC ,一般感染可考虑 3d 2次或 2d

司帕沙星与卤素反应产物的荧光特性及其应用

研究了卤素 (F ,Cl,Br ,I)与喹诺酮类药物司帕沙星反应产物的荧光特性 ,发现在酸性介质中 ,亚硝酸可氧化司帕沙星继而被卤素取代 ,所得产物具有强烈的荧光发射 ,其荧光强度随着卤素原子半径的增大呈现规律的增强效应。司帕沙星卤代物荧光较司帕沙星强 5 8～ 15 1倍。据此建立了卤素增强荧光光谱测定司帕沙星的新方法。该方法用于直接测定尿液中司帕沙星的含量 ,结果令人满意。本文还对司帕沙星的荧光增敏机理进行了探讨。

司氟沙星的合成

由五氟苯甲酸为原料，经酰氯化、与丙二酸二乙酯缩合、部分水解并脱羧、与原甲酸三乙酯缩合、环丙胺置换、环化、５－位苄氨取代、氢化去苄基、水解后与顺式－２，６－二甲基哌嗪缩合得司氟沙星，总收率３８％。

司氟沙星注射液治疗急性细菌感染60例

目的 :观察国产司氟沙星注射液 (SPFX)治疗急性细菌感染的疗效和不良反应。方法 :共治疗 6 0例患者 ,随机分为试验、对照及开放组各 2 0例 ,试验及开放组静脉滴注SPFX 2 0 0mg·d-1,qd ;对照组静脉滴注氧氟沙星注射液 (OFX) 4 0 0mg·d-1,bid ;疗程均为 5～ 14d。结果 :试验及开放组共 40例 ,总有效率和细菌清除率为 95 %和93 .5 % ;对照组 2 0例 ,总有效率和细菌清除率为 80 %和 88.9%。用药中不良反应较轻 ,试验及开放组发生率 5 % ,对照组发生率 10 %。结论 :本药治疗临床常见的中重度急性细菌性感染疗效高 。

司帕沙星人体药代动力学与相对生物利用度研究

目的：研究司帕沙星片在健康人体内的药代动力学与相对生物利用度。方法：采用反相高效液相色谱法测定１０名健康志愿者ｐｏ２００ｍｇ国产和进口的司帕沙星片后血药浓度变化情况，计算两者的药代动力学参数及相对生物利用度，并以ＡＵＣ０～∞，ｔｍａｘ，ｃｍａｘ为指标，用配对ｔ检验法分析国产片与进口片的生物等效性。结果：国产与进口司帕沙星片的药－时曲线可用二室模型拟合，其ＡＵＣ０～∞分别是：（２３．７３±２．１１）μｇ·ｈ·ｍｌ－１与（２３．９１±３．１８）μｇ·ｈ·ｍｌ－１；ｔｍａｘ分别是（３．１３±０．５４）ｈ与（２．８４±０．５６）ｈ，ｃｍａｘ分别是：（０．７０±０．０５）μｇ·ｍｌ－１与（０．７３±０．０５）μｇ·ｍｌ－１。配对ｔ检验结果表明：ＡＵＣ０～∞，ｔｍａｘ，ｃｍａｘ均无显著性差异（Ｐ＞０．０５）。结论：国产与进口司帕沙星片为生物等效制剂；国产司帕沙星片对进口片的相对生物利用度为（９７．８１±１３．６２）％。

司帕沙星的毛细管电泳高频电导法测定

采用毛细管电泳高频电导法检测了司帕沙星。探讨了缓冲液的种类、浓度、添加剂以及操作电压和进样时间等因素对分离的影响。选择3.0mmol LHAc-5.0%C2H5OH(V V)为电泳介质,分离电压20.0kV,在4min内可实现司帕沙星的分离检测。在优化条件下,司帕沙星的线性范围为6 0～280 0μg mL,检出限为1 9μg mL。在该条件下,片剂中的敷料不干扰测定,可成功测定片剂中的司帕沙星,样品回收率为98.7%～101%。

司帕沙星金属络合物在胶束体系中的荧光特性研究及应用

研究了在金属离子存在下司帕沙星在胶束体系中的荧光特性，首次发现锌（Ⅱ）和阴离子表面活性刑十二烷基硫酸钠对司帕沙星的荧光有显著的协同增敏作用。据此建立了测定人体尿液中司帕沙星含量的同步-导数荧光光谱法，定量线性范围为0．04－4．0mg／L，检测限为0．04mg/L。相对标准偏差为1．6％－3．9％。探讨了锌（Ⅱ）和十二烷基硫酸钠对司帕沙星荧光的增敏机理。