Drug impurities identification

Tollsten L. HPLC/MS for drug impurity identification. In Gorog S, ed. Identification and Determination of Impurities in Drugs. New York Elsevier, 2000 266-297. 

Tollsten, L. 1TPLC/MS for drug impurity identification. Prog. Pharm. Biomed. Anal. 4 266-298, 2000. 

So-called street drugs for identification of principal components, impurities, adulterants, and cutting agents in order to establish the method of synthesis, to compare the samples seized from users with those from dealers, as well as for comparative analysis or so-called profiling to find out the source of the material. 

Solutions to practical problems rarely depend upon a single technique or a single approach. The following example of an impurity identification in a pharmaceutical product illustrates the key role that LC-MS can play in such an investigation, but also illustrates the limitations of the technique. The identification of this impurity has been published elsewhere in complete detail [75]. The problem and solution is summarized here. The impurity, designated as H3, was observed at 0.15% in a bulk lot of the drug substance in the structure below. The impurity required identification before the bulk lot could be released for use in further studies. 

Capillary zone electrophoresis (CZE) is the most common electrophoretic separation technique due to its simplicity of operation and its flexibility. It is the standard mode for drug analysis, identification of impurities, and pharmacokinetic studies. Other separation modes, such as capillary isotachopho-resis (CITP), micellar electrokinetc chromatography (MEKC), capillary electrochromatography (CEC), capillary gel electrophoresis (CGE), capillary isoelectric focusing, and affinity capillary electrophoresis (ACE), have then-advantages in solving specific separation problems, since the separation mechanism of each mode is different. 

Mol, R., Kragt, E., Jimidar, I., De Jong, G.J., Somsen, G.W. Micellar electrokinetic chromato-graphy-electrospray ionization mass spectrometry for the identification of drug impurities. J. Chromatogr. B 843, 283-288 (2006)... 

B. C. M. Potts, K. F. Albizati, M. O Neil Johnson, and J. P. James, Applications of LC-NMR to the identification of bulk drug impurities in GART inhibitor AG2034, Magn. Reson. Chem. 37 (1999), 397 00. 

This multidisciplinary team approach toward impurity identification was successfully applied to the identification of this impurity. Each and every discipline played a very important role. Without SPE enrichment to remove the drug substance from the impurities, the impurity could not be purified by preparative HPLC. The novel acidic degradation study of the impurity provided very valuable information of the structure of the impurity. Mass spectrometry and nuclear magnetic resonance spectroscopy were the ultimate tools in this structure elucidation. Furthermore, the formation mechanisms were concluded by a careful examination of the process. 

Fig. 6.14 Application of Raman nnciospectrometry to TLC drug spot identification (top trace) and impurity identification (bottom trace). Reproduced with permission from C.J. Fmnk. Raman Spectroscopy for Identity Testing [18] published by SPIE 1999.

Identification and Quantification of Impurities in Drugs Impurities Resulting from the Synthesis Pathway... 

Some applications for which NMR has been used in forensic analysis include the identification of compounds by comparison of spectra with those of authentic materials, the determination of structures of unknown compounds such as designer drugs, the identification of impurities in illicit drugs, the determination of optical purity of drugs, and the characterization of explosives, accelerants, fire residues, and various body fluids or tissue extracts. This article will briefly review each of these applications. 

If the objective is identification (qualitative analysis), it suffices to compare the spectrum of the analyte with that of a standard, both recorded in the same solvent and at an identical pH. This is not the main application of UV-Vis spectrophotometry as the best results in this context are provided by spectroscopic methods considered more effective for the study of the molecular structure of organic compounds (infrared, nuclear magnetic resonance, mass spectrometry, and X-ray diffraction). However, UV-Vis spectrophotometry is a source of relevant supplementary information that helps in the elucidation of molecular structures of drugs, impurities, metabolites, intermediate compounds of degradation, etc. 

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