Rapid Determination of Ranitidine in Human Plasma by Liquid Chromatography-Tandem Mass Spectrometry and Its Application to a Clinical Pharmacokinetic Study

A rapid and sensitive assay based on high performance liquid chromatography-tandem mass spectrometry（LC-MS/MS） was developed for the determination of ranitidine（RAN） in human plasma with codeine as internal standard（IS）.After protein precipitation with acetonitrile,the analyte and IS were separated on a Zorbax SB-Aq C18 column（150 mm×4.6 mm i.d.,5 μm） eluted with a mobile phase consisting of methanol/acetonitrile/10 mmol/L ammonium acetate containing 1% formic acid（pH=2.4）（volume ratio 12.5：12.5：75） at a flow rate of 1.0 mL/min.Detection was performed by electrospray ionization in the positive ion mode followed by the multiple reaction monito-ring（MRM） of the transitions of RAN at m/z 315.1→176.3 and of IS at m/z 300.1→165.1.The method was linear over a concentration range of 1―1000 ng/mL（r=0.9991） with a lower limit of quantitation（LLOQ） of 1 ng/mL and a limit of detection（LOD） of 0.3 ng/mL.Accuracy as relative error was from-0.01% to-1.7% and intra-day and inter-day precisions as relative standard deviation were ≤8.9% and ≤5.5%,respectively.The method was successfully applied to a pharmacokinetic study of ranitidine,getting a single oral dose（160 mg） to healthy volunteers.

Determination of Acetonitrile Volume Fraction in Mobile Phase by HPLC

This paper reports the development and validation of an assay for the determination of acetonitrile in the recycled mobile phase using high performance liquid chromatography（HPLC）. The method is based on that the retention in reversed-phase liquid chromatography increases with decreasing concentration of organic phase in the mobile phase. The natural logarithm of the capacity ratio for a given solute is linearly related to the volume fraction of the organic modifier in the mobile phase. For dimethylphthalate and diethylphthalate, the linearity range is 30%--60%, and for biphenyl and terphenyl, the range is 60%--95%. Precision values（RSD） were both 〈1% and the accuracy（RE） was in the range of ±1%. The assay was successfully applied to the determination of acetonitrile concentration of recycled mobile phase after the distillation of the column eluent in our laboratory.

Liquid Chromatography-Electrospray Quadrupole Linear Ion Trap Mass Spectrometric Method for Quantitation of Domperidone in Chinese Healthy Volunteers

A rapid, sensitive, and accurate method based on LC/MS/MS was developed and validated for the determination of domperidone in human plasma. Domperidone and internal standard, tramadol, were extracted from plasma with di- ethyl ether-dichloromethane （60： 40, volume ratio） and separated by reversed-phase HPLC with methanol-water-am- monia solution（80： 20： 0.2, volume ratio） as the mobile phase. Detection was carried out v/a multiple-reaction moni-toting（MRM） on a Q-trap^TM LC/MS/MS system（Q-trap^TM）. The assay result was linear over a concentration range of 0.1-30 ng/mL with a limit of quantitation （LOQ） of 0.1 ng/mL. The inter-and inn＇a-day precision levels were within 7.52% and 12.9%, respectively, whereas the accuracy was within a range of 87.3%-114%. This method has been successfully applied to evaluate the pharmcokinetics of domperidone in Chinese healthy volunteers given an oral dose of 10 mg.

基于淋巴系统的药物及其递送系统研究进展

近年来,位于淋巴系统的生物学靶标越来越多地被发现和利用;以调控淋巴系统功能或纠正淋巴系统病理改变为主要作用机制的药物逐渐成为研发热点之一;药物经淋巴系统的吸收、转运、代谢与递送研究与相应递送系统的开发也正引起重视。很多研究成果正被尝试用于免疫治疗、炎症调控、新型疫苗等重要领域,为肿瘤、自身免疫病、感染类疾病、代谢综合征等多类别重大疾病的治疗带来新机会。本文简要介绍了淋巴系统的结构与生理功能,淋巴系统内药物靶标与相关药物研究,以及药物经淋巴系统转运的模式与递送技术,希望给药学科学工作者、产业界和监管科学界专业人士提供参考。