The use of gas chromatography for determining pharmaceutical residues in clinical, cosmetic, food and environmental samples in the light of the requirements of sustainable development

Abstract

The sustainable development of human activities is directly related to the protection of the environment by lowering the anthropogenic stress. Pharmaceuticals – due to their growing consumption (use in medicine, veterinary, animal production, cosmetics) and their incomplete removal in wastewater treatment plants – are classifi ed as a group of new and rapidly emerging pollutants which have been proven to have a negative impact onto water organisms. In order to ensure the proper protection of human health and the environment there is an urgent necessity of determining pharmaceuticals in clinical, cosmetic, food and environmental samples. Gas (GC) and high performance liquid chromatography (HPLC) are valuable techniques for such determination, especially when they are coupled with mass spectrometry (GC-MS; LC-MS) or tandem mass spectrometry (GC-MS/MS; LC-MS/MS). The purpose of this paper is to present an analysis of sustainability features of analytical techniques in the light of necessity to determine trace amounts of pharmaceuticals in the aforementioned different matrices. Using the Delphi method we performed an analysis of the key sources of the competitive advantages of the application of GC and GC-MS techniques for determining the pharmaceutical residue in clinical, cosmetic, food and environmental samples – compared to techniques based on HPLC or LC-MS. The analysis covered the following areas: (i) the features of the technique, (ii) the price, and (iii) the applicability in various sectors of economy. The use of gas chromatography for determining pharmaceutical residues in clinical, cosmetic, food and environmental... 43 as volatile derivatives (30%) (own calculation). For the remaining 65% of the pharmaceuticals, the technique used most frequently is HPLC or LC-MS/MS. Table 1 summarizes the most important attributes in favor of using the GC and the GC-MS techniques compared to LC-based techniques. Gas chromatography is classifi ed as a high-resolution technique. This is mainly due to the many times higher effi ciency of GC columns, in relation to columns used in LC. The large number of the analytes possible to be determined in one chromatographic run directly infl uences the reduction of Table 1. Analysis of the key sources of the competitive advantage of GC compared to LC techniques, in relation to its attributes No. The source of competitive advantage Rating of the advantage Characteristic 1 Uniqueness of the service Signifi cant for 35% of pharmaceuticals The existing demand for determination of pharmaceuticals using GC is not large. Literature data also indicates a dominant share of the LC technique used in such analyses, e.g.: according to Scopus, as of 30.01.2018, 3874 reports on the analyses of pharmaceutical residues using the GC technique and respectively 18137 reports using the LC technique were recorded. It should be underlined, that when determinations must be carried out in regulated fi elds, the selection of the measuring technique is regulated by the legal requirements. In other areas, meteorological requirements, availability of equipment and personnel qualifi cations are decisive. Summing up, few companies identify residuals of pharmaceuticals using GC and GC-MS, hence the uniqueness of the availability of the service for 35% of the pharmaceuticals can be signifi cant. 2 Duration of the analysis Average Time of chromatographic ‘run’ depends on the number of analytes taken as targets and MS abilities. When comparing the GC and LC analysis of for example 20 pharmaceuticals, the time of analysis is very comparable. This means that the advantage of the GC and the GC-MS techniques in this area is not signifi cant. 3 Availability of the technique Average High availability of GC and GC-MS as well as of HPLC and LC-MS equipment in the market and in laboratories causes the prevalence of the GC-based techniques in this area to be insignifi cant. 4 Accuracy of the result Signifi cant High accuracy of the obtained result is attributable to a far lower matrix effects affecting the results of fi nal determinations, in comparison to the analyses using LC-MS (Caban et al. 2012). It is associated with the technique ion source used. Electron Ionization (EI, in case of GC-MS) is less sensitive to matrix effects compared to Electro-Spray Ionization (ESI) (used routinely in LC-MS) (Biswas and Mitra 2013). It is important because certifi ed reference materials (Certifi ed Reference Materials – CRMs) of adequate quality are practically unavailable for a large part of the analyses and matrices, therefore having patterns of appropriate quality as well as an adequately optimized methodology is crucial for obtaining a highly accurate result. The examples of negative matrix impact onto chromatographic analysis can be found in literature (Caban et al. 2012, Garrido et al. 2009). In general, the GC-MS maintained in clear conditions are much less affected by matrix effects, compared to LC-MS. This results in more accurate and reliable results. 5 Detection limits Average Sensitivity of the GC-MS technique is comparable to the LC-MS. It is also suffi cient in terms of the expected necessary concentration ranges (ng/l or ng/kg), however, application of SPE-GC is associated with a higher concentration ratio of the sample, e.g. transfer of the analytes from a 500 ml sample to a 0.1 ml volume (the volume of the derivatising agent) gives a concentration factor of 5000 (Caban et al. 2016); for this type of analyses SPE-LC-MS most commonly is 500. An advantage of GC and GC-MS in this area, however, is not signifi cant and obtained pharmaceuticals detection limits derive mostly from extraction techniques applied (Liška and Slobodník 1996). 6 Waste production Signifi cant Low waste production, in comparison to the LC-MS technique, is associated with application of a carrier gas as a mobile phase. Such method additionally is much cheaper and environmentally friendly, because there is no need for disposal of the solvent wastes. Consumption of solvents in the techniques of HPLC nowadays can be limited up to 90% (Caban et al. 2015), however, the cost of such solutions is many times higher. GC is often so-called green technique in chromatography (Biswas and Mitra 2013). 7 The rate of implementation in routine analyses Signifi cant Much faster to be implemented for routine analyses in environmental and biomedical laboratories, in comparison with LC-MS-based methods. It results from the lower cost (see Table 2). In addition, the time needed to train a worker to operate GC-MS equipment is shorter due to easier optimization of this system’s operation. Source: own elaboration 44 J. Sadkowska, M. Caban, M. Chmielewski, P. Stepnowski, J. Kumirska the price of obtaining a single piece of analytical information. Although the resolution is much better in chromatographic part of GC-MS than in LC-MS, it is diffi cult to talk about competitiveness, since in typical target analyses, such as determining pharmaceutical residues, determination of analytes is based on mass spectrometric detection e.g. on monitoring a selected ion-fragmentation (SIM) or on multiple fragmentation (multiple reaction monitoring mode – MRM) instead of chromatographic parameters. For this reason, nowadays the overlap of analyte signals during chromatographic separation is no longer a big problem. Higher resolution of GC has become, however, a defi nite advantage when much simpler detectors are used instead of a mass spectrometer. The GC and the GC-MS techniques are characterized by very small, in comparison to HPLC and LC-MS, amount of waste generated during analyses. The consumption of carrier gases in relation to the consumption of organic liquid phases is also many times cheaper and environmentally friendly. Although solvent consumption in liquid chromatography presently is limited due to introduction of ultra-performance systems (Caban et al. 2012) allowing for the reduction of the amount of the mobile phase even by 90%, the cost of such solutions is many times higher. In 2015, we conducted a study using a diagnostic survey method, which encompassed 277 Polish institutions and other entities employing in their activities analytical methods (Sadkowska et al. 2017). The aforementioned institutions included fi rst of all selected laboratories, research institutes as well as the laboratories operating within the structures of higher education. Although chromatographic techniques were used by a relatively high number of the studied institutions and enterprises (private and public), the analyses confi rmed that determination of the residues of pharmaceuticals in environmental, food and clinical samples is performed by a small group of entities (a total of 62 entities). 7 entities confi rmed to have analyzed the residues of pharmaceuticals in environmental samples, 13 entities in food samples, 12 entities in clinical samples, and 30 entities in other matrices. The studied entities indicated that their decision to select GC-MS technique instead of LC-MS was driven, among other factors, by the cost of equipment. The other group of respondents confi rmed that they preferred to use the services of external laboratories because in the case of performing not too many analyses, it was cheaper than purchasing and operating GC-MS / LC-MS equipment. It was also interesting to observe that GC as an analytical techniques were used mainly by the veterinary inspectorates as well as institutions controlling water and food quality. The key sources of the competitive advantage of GC and GC-MS in terms of the price In many cases, the decisive factor in applying a given solution by an analytical unit is its total cost, calculated as the sum of expenditures that are necessary to purchase the equipment as well as the sum of operating costs (services, consumables, energy etc.). The strengths characterizing GC and GC-MS in respect to this area are presented in Table 2. In the case of GC and GC-MS,