Chemometrics in pharmaceutical analysis

Chemometrics is a science where chemistry and pharmaceutical science meet statistics and software. The primary focus of chemometrics involves the use of mathematical or software procedures in particular, both to develop analytical methods and to analyse the signals and results obtained. This paper focusses on chromatography and on how chemometrics has been applied to chromatographic problems in pharmaceutical and biomedical analysis. Examples of several chemometric techniques are given and recent developments in the use of optimization methods, regression methodology, multivariate analysis and expert systems are discussed.     

Application of Gran's potentiometric method in pharmaceutical analysis.

Because of weak acid-base properties, many pharmaceuticals cannot be determined by the convenient neutralization titrimetric method. It is shown that such substances can be precisely analyzed by applying the graphic pH-potentiometric method of Gran. Some water-soluble and insoluble pharmaceuticals, which usually are analyzed in nonaqueous solvents, have been determined precisely in water solution by this method. The latter is also applied successfully to the analysis of mixtures and impurities in pharmaceuticals.     

液相色谱-四级杆-飞行时间质谱联用技术在药物分析中的应用

本文介绍了液相色谱-四级杆-飞行时间质谱联用(LC-Q-TOF MS)技术近年来的研究进展,综述了该方法在药物中的有关物质分析、非法添加化学成分的鉴定分析、代谢组学及中药学4个主要方面的应用及其研究进展。     

药物科学研究中药物分析学的应用

药物分析学的观念不断更新,研究范围不断拓宽,并作为药物科学研究的工具和眼睛,贯穿于工业药学和临床药学研究的始终。本文介绍和总结了药物分析技术在药物研究与开发过程、药物生产过程和药物使用过程中的进展和应用,着重介绍了过程分析技术在药物生产过程中的应用。     

Application of Prussian blue-based optical sensor in pharmaceutical analysis.

Optical flow-through cell-detector with incorporated transparent chemosensitive layer of Prussian blue has been applied in simple, single-channel flow-injection system for pharmaceutical analysis. The reductant analyte converts the Prussian blue based sensing layer to Prussian white form, and the attendant color change is used for sensing. Discoloration of the film is spectrophotometrically detected at 720 nm wavelength. The flow injection system has been successfully used for selective determination of ascorbic acid in simple and complex pharmaceuticals. The method is free from interferences caused by various ions and active ingredients commonly found in pharmaceuticals. The flow-through sensor is useful for spectrophotometric flow-injection analysis of intensively colored and turbid samples. The results of medicine analysis are comparable to those obtained using reference pharmacopeal method. The analytical system could be also used for determination of cysteine and hydrogen peroxide in medicines.     

Prevalidation in pharmaceutical analysis. Part I. Fundamentals and critical discussion

A complete prevalidation, as a basic prevalidation strategy for quality control and standardization of analytical procedure was inaugurated. Fast and simple, the prevalidation methodology based on mathematical/statistical evaluation of a reduced number of experiments (N < or = 24) was elaborated and guidelines as well as algorithms were given in detail. This strategy has been produced for the pharmaceutical applications and dedicated to the preliminary evaluation of analytical methods where linear calibration model, which is very often occurred in practice, could be the most appropriate to fit experimental data. The requirements presented in this paper should therefore help the analyst to design and perform the minimum number of prevalidation experiments needed to obtain all the required information to evaluate and demonstrate the reliability of its analytical procedure. In complete prevalidation process, characterization of analytical groups, checking of two limiting groups, testing of data homogeneity, establishment of analytical functions, recognition of outliers, evaluation of limiting values and extraction of prevalidation parameters were included. Moreover, system of diagnosis for particular prevalidation step was suggested. As an illustrative example for demonstration of feasibility of prevalidation methodology, among great number of analytical procedures, Vis-spectrophotometric procedure for determination of tannins with Folin-Ciocalteu's phenol reagent was selected. Favourable metrological characteristics of this analytical procedure, as prevalidation figures of merit, recognized the metrological procedure as a valuable concept in preliminary evaluation of quality of analytical procedures.     

Mirror images: the analysis of pharmaceutical enantiomers.

Pharmaceutical enantiomers often exhibit different pharmacodynamic and pharmacokinetic properties. Stereospecific chromatographic assays are available to separate these stereoisomers. Therapeutic agents often contain chemical functional groups (e.g. amino, hydroxyl, carbonyl, and carboxylic acid). These can be reacted with enantiomerically pure reagents to give diastereoisomers suitable for analysis on achiral gas chromatographic (GC) and high performance liquid chromatographic (HPLC) columns. Alternatively, derivatized or underivatized drugs may be resolved on chiral chromatographic phases. A wide variety of GC (e.g. amino acid, cyclodextrin, and metal-complex) and HPLC (mobile phase additive, crown ether, pi-pi interaction and related phases, protein, cyclodextrin, polysaccharide, methacrylate and amide polymer, and ligand exchange) columns are commercially available. This article reviews the chromatographic separation of enantiomers.     

GLC analysis of caffeine and codeine phosphate in pharmaceutical preparations.

A procedure for the determination of caffeine and codeine phosphate in pharmaceutical preparations was developed. It depends upon a one-step extraction followed by GLC analysis by the concentrated extract.     

Validation in pharmaceutical analysis. Part I: an integrated approach

The ICH guidelines achieved a great deal in harmonising the definitions of the required validation characteristics and their basic requirements. However, they provide only a basis for a general discussion of the validation parameters, their calculation and interpretation. It is the responsibility of the analyst to identify parameters which are relevant to the performance of the given analytical procedure as well as to design proper validation protocols including acceptance criteria and to perform an appropriate evaluation. In order to fulfil this resposibility properly, the background of the validation parameters and their consequences must be understood. In this part, the general concept of an integrated validation is discussed. The interdependencies to other ICH guidelines and topics during drug development (e.g. impurities and degradants, stability and specification design) must be taken into account to define the required acceptance criteria. Evaluation of the results in order to prove the suitability of the analytical procedure must be based on the specification limits. Important parameters and aspects are discussed for the individual validation characteristics. In the following parts, these parameters will be discussed in detail. Examples will be given for their interpretation in order to facilitate the selection of parameters which are relevant to the performance and suitability of the given analytical procedure.     

New derivatization reactions in pharmaceutical analysis

The application of chemical reactions in conjunction with spectrometric and chromatographic methods is exemplified by the formation of 2-nitrophenylhydrazide derivatives for the spectrometric assay of carboxylic acids; silylation and trifluoroacetylation of drugs for gas chromatography; selective reduction of steroid ketones for their IR spectrometric identification; the use of epoxidation in discriminating between saturated and unsaturated steroids in gas chromatography; increasing the selectivity and sensitivity of the spectrometric and gas chromatographic determination of isomeric Delta4- and Delta5-3-ethylenedioxy steroids by treatment with hydrochloric acid; and the use of the same reagent in the difference spectrometric determination of 2,5-dimethyl-alpha-ethyl benzhydrol.     

液相色谱-核磁共振联用技术在药物分析中的应用

液相色谱(LC)是分离复杂混合物的较好方法,核磁共振(NMR)是结构分析的强有力工具.液相色谱-核磁共振(LC-NMR)联用技术是快速分离、确定结构的一种分析手段,具有广阔的应用前景.主要综述了LC-NMR联用技术在化学药物分析(包括未知杂质的结构分析、混合物中已知成分的定量分析)、中药及天然药物分析(包括异构体分析、新化合物的结构鉴定)、海洋生物及生化大分子、代谢产物分析中的应用.     

Advances in automation of pharmaceutical analysis

The development of a new drug substance and its dosage forms demands the establishment and implementation of suitable analytical methods. Through the application of chemometrics, “intelligent” laboratory systems and integrated data handling systems, considerable progress is being made in automating both the development and routine use of analytical methods in pharmaceutical analysis.