高效液相色谱-四极杆/飞行时间高分辨质谱测定化妆品中的西咪替丁及雷尼替丁

建立了化妆品中西咪替丁及雷尼替丁的高效液相色谱-四极杆/飞行时间高分辨质谱检测方法,并对其质谱裂解规律进行研究。待测样品经甲醇超声提取,过滤膜后经Zorbax SB-Aq色谱柱(3.0 mm×100 mm,1.8μm)分离,用乙腈-含0.1%甲酸的水溶液梯度洗脱后,在双喷雾电喷雾离子源正离子模式下检测,数据采集使用一级母离子全扫描和目标二级离子扫描。在不同的化妆品基质中,西咪替丁和雷尼替丁分别在5.65～113 ng/mL和4.95～99.0 ng/mL范围内线性关系良好(r0.999),检出限分别为1.1、0.99 ng/mL,定量下限分别为5.6、5.0 ng/mL;2种待测物在低、中、高3个加标水平下的回收率为86.7%～110%,相对标准偏差(RSD)为0.90%～6.0%,方法重复性良好(RSD10%)。该方法前处理简单,灵敏度较好,线性、回收率及重复性均满足方法学要求,可用于化妆品中西咪替丁和雷尼替丁的筛查测定。     

Preparation of Co-Processed Excipients for Controlled-Release of Drugs Assembled with Solid Lipid Nanoparticles and Direct Compression Materials

The purpose of the study was to develop a novel, directly compressible, co-processed excipient capable of providing a controlled-release drug system for the pharmaceutical industry. A co-processed powder was formed by adsorption of solid lipid nanoparticles (SLN) as a controlled-release film onto a functional excipient, in this case, dicalcium phosphate dihydrate (DPD), for direct compression (Di-Tab^®). The co-processed excipient has advantages: easy to implement; solvent-free; industrial scaling-up; good rheological and compressibility properties; and the capability to form an inert platform. Six different batches of Di-Tab^®:SLN weight ratios were prepared (4:0.6, 3:0.6, 2:0.6, 1:0.6, 0.5:0.6, and 0.25:0.6). BCS class III ranitidine hydrochloride was selected as a drug model to evaluate the mixture’s controlled-release capabilities. The co-processed excipients were characterized in terms of powder rheology and dissolution rate. The best Di-Tab^®:SLN ratio proved to be 2:0.6, as it showed high functionality with good flow and compressibility properties (Carr Index = 16 ± 1, Hausner Index = 1.19 ± 0.04). This ratio could control release for up to 8 h, so it fits the ideal profile calculated based on biopharmaceutical data. The compressed systems obtained using this powder mixture behave as a matrix platform in which Fickian diffusion governs the release. The Higuchi model can explain their behavior.     

顶空液相微萃取-气相色谱法测定盐酸雷尼替丁中二氯甲烷和三氯甲烷的残留量

采用顶空液相微萃取与气相色谱联用技术测定雷尼替丁中二氯甲烷和三氯甲烷的残留量。自制了萃取液保护装置。考察了萃取溶剂的种类、萃取时间、萃取温度、萃取液的体积对二氯甲烷和三氯甲烷萃取效果的影响。以正十三烷为萃取剂,在60 ℃下萃取30 min,萃取液滴体积2 μL。二氯甲烷含量在1～10 μg/g范围内与色谱峰高呈线性关系,相关系数(r2)为0.9733;三氯甲烷含量在1～10 μg/g范围内与色谱峰高呈线性关系,r2为0.9724。二氯甲烷和三氯甲烷的最低检出限分别为0.0273 μg/g和0.0410 μg/g,加标回收率分别为93.6%～102%和98.1%～103%。方法简便易行,测定结果准确。     

In Vitro Investigation on Interaction of Ranitidine Hydrochloride in the Presence of Cross-Linked Carboxymethyl Cellulose Sodium.

Summary: The adsorbance of ranitidine hydrochloride – drug selective H₂ histamine receptor inhibitor used In the treatment of gastric and duodenal ulcer was investigated in the presence of croscarmellose, a cross- linked polymer of polysaccharide character used as a swelling additive in oral pharmaceutical formulations – capsules, tablets and granules. The evaluation of adsorbance capability was carried out by means of a statistical method in in vitro conditions, taking into account environmental pH, concentration of the investigated drug as well as the properties of the polymer. Obtained results prove that the analyzed active agent is adsorbed on polymer at all the investigated pH ranges and the capability of polymer binding depends on environmental pH. The highest binding capability was revealed in samples with pH of 7.6, (adsorbance capacity k = 0.6958) while the lowest binding capability was observed at pH 1.5 (adsorbance capacity k = 0.0005) in the presence of croscarmellose sodium. Level of adsorption depends on the analyzed drug concentration and adsorption on polymer in increasing concentration and pH environment.     

制剂药品中盐酸雷尼替丁含量测定方法的优化

建立高效液相色谱仪测定盐酸雷尼替丁制剂含量的检测方法。采用磷酸盐缓冲液与乙腈等比混合的流动相等度洗脱,于314 nm检测,外标法定量。盐酸雷尼替丁质量浓度在5～500μg/mL范围内与色谱峰面积线性相关,相关系数大于0.999 9。6次测定结果的相对标准偏差为0.85%,加标回收率为(100±2)%。该法操作简便、清洁高效、准确可靠,可用于盐酸雷尼替丁片和胶囊含量的测定。     

Applicability of Derivative Spectrophotometry,Bivariate Calibration Algorithm,and the Vierordt Method for Simultaneous Determination of Ranitidine and Amoxicillin in Their Binary Mixtures

Abstract

Ultraviolet (UV)–derivative spectrophotometry, bivariate calibration algorithm, and Vierodt methods were applied to simultaneous determination of ranitidine (R) and amoxicillin (AMX) in binary mixtures. The first-order derivative allows determination of R in the concentration range 4.0 · 10^?6 mol · dm^?3 to 6.0 · 10^?5 mol · dm^?3. Vierordt method enables Ranitidine assaying in the presence of 2.5-fold excess of AMX and 3-fold excess of R. The bivariate calibration method obeys Beer's law in the concentration ranges 4.0 · 10^?6 mol · dm^?3 to 6.0 · 10^?5 mol · dm^?3 for R and 2.0 · 10^?6 to 2.0 · 10^?5 mol · dm^?3 for AMX.     

Kinetic Spectrophotometric Determination of Ranitidine

Two spectrophotometric methods were developed for the determination of ranitidine. The first method was a kinetic spectrophotometric method based on the catalytic effect of ranitidine on the reaction between sodium azide and iodine in an aqueous solution. The calibration graph was linear from 4–24 μg/mL. The drug was determined by measuring the decrease in the absorbance of iodine at 348 nm using a fixed time method. The decrease in the absorbance after 1 minute from the initiation of the reaction was related to the concentration of drug. The detection limit of the procedure was 0.76 μg/mL. The proposed procedure was successfully utilized in the determination of the drug in pharmaceutical preparations with mean recovery in the range of 99.83 ? 101.16%. The second method is a colorimetric method, which depends on the measurement of absorbances of tris (o‐phenanthroline) iron(II) [method 2A] and tris (bipyridyl) iron(II) [method 2B] complexes at 512 nm. The complexes obeyed Beer's law over the concentration range of 2–16 μg/mL and 4–40 μg/mL for methods 2A and 2B, respectively. The developed method has been successfully applied for the determination of ranitidine in bulk drugs and pharmaceutical formulations. The common excipients and additives did not interfere in its determination.     

Indirect Determination of Ranitidine Hydrochloride Using a Chloride Ion Selective Electrode

Abstract

A simple, rapid, and reliable potentiometric method is described for determination of ranitidine hydrochloride in pharmaceutical formulations. Experiments were performed to determine the suitability of using a chloride-ion selective electrode for the indirect estimation of ranitidine hydrochloride. The precision and accuracy of the potentiometric method were determined. We found that they not differ significantly. The advantage of the proposed method is the fact that it can be applied without filtration of the drug sample before analysis.     

Pharmaceutical polymorphs quantified with transmission Raman spectroscopy

The quantification of polymorphs in dosage forms is important in the pharmaceutical industry. Conventional Raman spectroscopy of solid‐state pharmaceuticals may be used for this, but it has some limitations such as sub‐sampling and fluorescence. These problems can be mitigated through the use of transmission Raman spectroscopy (TRS). The efficacy of TRS measurements for the prediction of polymorph content was evaluated using a ranitidine hydrochloride test system. Four groups of ranitidine hydrochloride‐based samples were prepared: three containing form I and II ranitidine hydrochloride and microcrystalline cellulose (spanning the ranges 0–10%, 90–100% and 0–100% form I fraction of total ranitidine hydrochloride), and a fourth group comprising form I ranitidine hydrochloride (0–10%) spiked commercial formulation. Transmission and conventional Raman spectroscopic measurements were recorded from both capsules and tablets of the four sample groups. Prediction models for polymorph and total ranitidine hydrochloride content were more accurate for the tablet than for the capsule systems. TRS was found to be superior to conventional backscattering Raman spectroscopy in the prediction of polymorph and total ranitidine hydrochloride content. The prediction model calculated for form I content across the 0–100% range was appropriate for process control [ratio of prediction to deviation (RPD) equal to 14.62 and 7.42 for tablets and capsules, respectively]. The 10% range calibrations for both form I and total ranitidine hydrochloride content were sufficient for screening (RPDs greater than 2.6). TRS is an effective tool for polymorph process control within the pharmaceutical industry. Copyright © 2011 John Wiley & Sons, Ltd.     

High-performance liquid chromatographic methods for the determination of ranitidine and its metabolites in biological fluids

Summary The use of an existing reversed-phase ion-pair method for the determination of ranitidine, ranitidine-N-oxide, ranitidine-S-oxide and desmethylranitidine in the plasma of patients taking the anti-ulcer drug, ranitidine is described. The development of a ternary reversed-phase system which is more suitable for the routine determination of ranitidine and the three metabolites is reported. This system has been used to determine quantitatively ranitidine and the metabolites in urine. Studies in animals using¹⁴C-ranitidine have shown that ranitidine is also oxidatively deaminated to a 5-substituted, 2-furan carboxylic acid. A reversed-phase ion-pair system, in which cetrimide is the counter ion, has been developed for the quantitative determination of the 5-substituted, 2-furan carboxylic acid and ranitidine-N-oxide in urine and faeces from patients treated with ranitidine. Presented at the 15th International Symposium on Chromatography, Nürnberg, October 1984