Chemical profiling of pharmaceuticals by capillary electrophoresis in the determination of drug origin

doi:10.1016/0021-9673(94)85223-5

Journal of Chromatography A

Volume 674, Issues 1–2, 15 July 1994, Pages 153-163

https://doi.org/10.1016/0021-9673(94)85223-5 Get rights and content

Abstract

Capillary electrophoresis has been utilized to detect trace components in bulk pharmaceutical products, with emphasis on the identification of differences among manufacturers that can be used for source verification in suspect/counterfeit cases. Micellar electrokinetic capillary chromatography with sodium dodecyl sulfate was used in the analyses of β-lactam antibiotics. The aminoglycoside clindamycin phosphate and the macrolide erythromycin stearate were analyzed using borate buffers with direct UV detection. Methyl-β-cyclodextrin was used as a buffer additive in the erythromycin studies. Determination of product potency using peak area ratios has been demonstrated for ampicillin and clindamycin phosphate.

References (24)

K.D. Altria
J. Chromatogr.
(1993)
C.-X. Zhang et al.
J. Chromatogr.
(1992)
M.C. Roach et al.
J. Chromatogr.
(1988)
K.D. Altria et al.
J. Chromatogr.
(1991)
K.D. Altria et al.
J. Chromatogr. A
(1993)
H. Nishi et al.
J. Chromatogr.
(1989)
C.E. Parker et al.
J. Am. Soc. Mass Spectrom.
(1992)
S.K. Yeo et al.
J. Chromatogr.
(1991)
S. Arrowood et al.
J. Chromatogr.
(1992)
H. Nishi et al.
J. Chromatogr.
(1990)

A.M. Arentoft et al.

J. Chromatogr. A

(1993)

R.J. Tait, P. Tan, D.J. Skanchy, D.O. Thompson, V.J. Stella, J.F. Stobaugh, D.W. Demarest and E.A. Mon-not-Chase,...

Cited by (54)

High-throughput screening of cocaine, adulterants, and diluents in seized samples using capillary electrophoresis with capacitively coupled contactless conductivity detection
2020, Talanta
Citation Excerpt :
However, few analytical techniques have the ability to determine, in a single run, both organic and inorganic species, without requiring instrumental changes. Capillary electrophoresis (CE) is a well-established analytical technique that has been applied for the determination of trace components in illicit drugs, including inorganic and organic compounds [11,22–27]. This technique offers several advantages, such as high sample throughput, high efficiency and resolution, as well as minimal reagents and sample consumption.
Cocaine is one of the most frequently used illicit drug in the world. Therefore, the development of simple and fast methods for the detection of cocaine and common adulterants, diluents and impurities are extremely important in forensic investigations. The present study describes, for the first time, a method based on capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C⁴D) for the rapid (2.5 min) and simultaneous quantification of cocaine, levamisole, lidocaine, carbonate, borate, chloride, nitrate, nitrite and sulphate. In the experiment, anions were separated in co-electroosmotic mode and cations in counter-electroosmotic mode employing a buffer solution composed by 10.0 mmol L⁻¹ TAPS, 12 mmol L⁻¹ NaOH and 0.2 mmol L⁻¹ CTAB as the background electrolyte (pH = 8.8). The developed CE method demonstrated some interesting analytical characteristics such as: (i) a simple sample pretreatment step (only dilution in water and filtering), (ii) high-throughput screening (24 injections h⁻¹), (iii) proper recovery values (between 72 and 118%), and (iv) an inter-day precision of less than 7% for all analytes. The procedure was successfully applied in the analysis of seized cocaine samples collected by the Integrated Forensics Post (PPI) of the Minas Gerais Civil Police (Uberaba, Minas Gerais State, Brazil), during the year of 2018.
Understanding and fighting the medicine counterfeit market
2014, Journal of Pharmaceutical and Biomedical Analysis
Citation Excerpt :
Most of the time lengthy methods based on chromatography have to be used. Capillary electrophoresis is an alternative method for liquid suspect counterfeits that enables to check the presence of a protein and its quality [85,86]. Time being a crucial factor for the detection of counterfeits, the use of vibrational spectroscopy for solid suspect counterfeits has increased within the last years.
Medicine counterfeiting is a serious worldwide issue, involving networks of manufacture and distribution that are an integral part of industrialized organized crime. Despite the potentially devastating health repercussions involved, legal sanctions are often inappropriate or simply not applied. The difficulty in agreeing on a definition of counterfeiting, the huge profits made by the counterfeiters and the complexity of the market are the other main reasons for the extent of the phenomenon. Above all, international cooperation is needed to thwart the spread of counterfeiting. Moreover effort is urgently required on the legal, enforcement and scientific levels. Pharmaceutical companies and agencies have developed measures to protect the medicines and allow fast and reliable analysis of the suspect products. Several means, essentially based on chromatography and spectroscopy, are now at the disposal of the analysts to enable the distinction between genuine and counterfeit products. However the determination of the components and the use of analytical data for forensic purposes still constitute a challenge. The aim of this review article is therefore to point out the intricacy of medicine counterfeiting so that a better understanding can provide solutions to fight more efficiently against it.
Counterfeit drugs detection by measurement of tablets and secondary packaging colour
2010, Journal of Pharmaceutical and Biomedical Analysis
The growth of pharmaceutical counterfeiting is a major public health problem. This growth is resulting in a proportional increase in the number of samples that medicines control laboratories have to test. Thus the need for simple and affordable preliminary screening methods to be used by inspectors to decide in the field whether to collect a sample for further laboratory analysis or not. This paper intends to evaluate the possibility to employ for preliminary examinations of suspicious samples an optical spectrophotometer (colorimeter) used in the graphic industry, capable of measuring the reflectance visible spectrum of solid materials. The colorimeter was tested on original and counterfeited Viagra, Cialis and Levitra by measuring the colour of tablets’ surface and of a specific spot of the packages. Various batches of the original drugs were employed both to investigate precision and robustness of the technique and to build spectral libraries. These libraries were used to compare suspicious samples to the corresponding original by means of a wavelength distance pattern recognition method. The method was eventually tested on suspicious samples sized by police authorities in order to evaluate its effectiveness. The device resulted precise and robust toward ambient conditions changes, although some limits emerged: the libraries of original samples need a frequent update and a lower precision is to be expected for tablets which surface is extremely convex.
Evaluation of the stability of gentamicin in different antibiotic carriers using a validated MEKC method
2008, Journal of Pharmaceutical and Biomedical Analysis
The quality control of gentamicin in different antibiotic carriers, using MEKC as stability-indicating method is described. Baseline separations of gentamicin C1, C1a, C2, C2a and C2b and, furthermore the impurities and degradation products garamin (GARA), 2-deoxy-streptamine (DSA) and sisomicin (SISO) were achieved with a background electrolyte containing 20 mM deoxycholic acid, 15 mM β-cyclodextrin and 100 mM tetraborate (pH 10.0). After derivatization with o-phthaldialdehyde reagent (OPA), UV detection at 340 nm was possible. The method was validated with respect to selectivity, limit of detection (LOD) and quantification (LOQ) of the impurities, linearity, accuracy, precision and robustness. Evaluation of four different antibiotic carriers stored under stability conditions according to the International Conference on Harmonization (ICH) guidelines and older pharmaceutical formulations disclosed good stability.
5 Role of CE in drug substance and drug product development
2008, Separation Science and Technology
Citation Excerpt :
Application fields are therefore as wide as the range of CE technologies. Some examples are the identification and categorization of seized drugs,27 counterfeit drugs,28 and cleaning verification.29,30 However, the most common use of CE identification methods remains in numerous applications for biosimilar synthetic drugs, such as small peptides31 and oligonucleotides32 and carbohydrates.33
The use of capillary electrophoresis (CE) during the synthetic drug development is described from the preclinical development phase to the final marketed stage. The chapter comprises the determination of physicochemical properties, such as acid−base dissociation constants (pK_a), octanol−water distribution coefficients (log P), and analysis of pharmaceutical counterions and functional excipients.
General requirements during clinical development and submission for CE methods, used for release, retest, and stability analysis, are illustrated by examples of CE applications. Guidelines for method development based on the nature of the analyte and the likelihood of a successful method development are given. Generic approaches and ready-to-use separation kits are described in order to minimize method development times. The specification setting process including examples for identity, purity, and assay tests is explained. Points to consider for a CE method transfer to another testing facility are discussed. Finally, further links to literature and review articles are referenced.
12 CE in impurity profiling of drugs
2008, Separation Science and Technology
Citation Excerpt :
MEKC was successfully employed for impurity profiling of batches of β-lactam antibiotics [ampicillin, amoxicillin, and phenoxymethylpenicillin (pen V)] and erythromycin stearate samples obtained from different pharmaceutical suppliers. Although the identity of the impurities is unknown, the impurity profile in terms of number of impurities and their respective levels allowed distinguishing samples from different manufacturers and can therefore be used as a fingerprint for source verification in suspect/counterfeit cases.233 MEKC permitted the separation of pen V234 as well as benzylpenicillin (PG)235 from their eight potential impurities.
This chapter illustrates possible applications of capillary electrophoresis in impurity profiling. Due to the large peak capacity of the technique, it is extremely well suited to separate the main drug compound from its possible impurities that often have a very related chemical structure. Moreover, the high efficiencies obtained, as well as the low reagent consumption make it a viable alternative to liquid chromatography in many cases of drug analysis.
After a short introduction into the relevance of impurity profiling for regulatory authorities, public health, and the pharmaceutical industry, an overview is presented based on the various modes of capillary electrophoresis that have been used in drug impurity analysis. The applications of capillary zone electrophoresis, non-aqueous capillary electrophoresis, micellar electrokinetic capillary chromatography, microemulsion electrokinetic capillary chromatography, capillary gel electrophoresis, and capillary electrochromatography are presented consecutively.

View all citing articles on Scopus

View full text

Chemical profiling of pharmaceuticals by capillary electrophoresis in the determination of drug origin

Abstract

J. Chromatogr.

J. Chromatogr.

J. Chromatogr.

J. Chromatogr.

J. Chromatogr. A

J. Chromatogr.

J. Am. Soc. Mass Spectrom.

J. Chromatogr.

J. Chromatogr.

J. Chromatogr.

J. Chromatogr. A