Upravljanje resursima u HPLC: Otkrivanje zelenog lica farmaceutske analize

High-pressure liquid chromatography (HPLC) is a technique of paramount importance in the analysis of pharmaceuticals because of its ability to separate moderately polar to less polar compounds, such as drugs and related substances. The concept of green analytical chemistry (GAC) aims to provide more environmentally friendly and safer analytical methods in terms of reagents, energy, and waste. One of the major challenges of GAC is to find an appropriate approach to evaluate the greenness of analytical methods. An extension of GAC, called white analytical chemistry (WAC), has been introduced to consider not only environmental friendliness, but also other aspects that contribute to the sustainability of methods, such as analytical and economic or practical efficiency. HPLC methods are intrinsically not green, due to the high consumption of toxic organic solvents and the resulting generation of large amounts of toxic waste. Fortunately, there are many approaches to overcome the non-green character of HPLC methods. In this article, various modifications of the HPLC methods that increase its environmental friendliness are presented, as well as the various tools used to evaluate environmental friendliness. In addition, the new concept of white analytical chemistry is presented.Tečna hromatografija pod visokim pritiskom (HPLC) je tehnika od ogromne važnosti u analitici lekova zbog svoje mogućnosti da razdvoji umereno do manje polarna jedinjenja, kao što su aktivne farmaceutske i srodne supstance. Koncept zelene analitičke hemije (GAC) ima za cilj da obezbedi ekološki prihvatljivije i bezbednije metode u pogledu reagenasa, energije i otpada. Jedan od glavnih izazova GAC je da pronađe odgovarajući pristup za procenu "zelenosti" analitičkih metoda. Proširenje GAC, nazvano bela analitička hemija (WAC), uvedeno je kako bi se uzela u obzir ne samo ekološka prihvatljivost, već i drugi aspekti koji doprinose održivosti metoda, kao što su analitička i ekonomska ili praktična efikasnost. HPLC metode suštinski nisu "zelene" zbog obimne potrošnje toksičnih organskih rastvarača i posledičnog stvaranja velikih količina toksičnog otpada. Srećom, postoji mnogo pristupa za prevazilaženje ne-zelene prirode HPLC metoda. U ovom radu su predstavljene različite modifikacije HPLC metode koje povećavaju ekološku prihvatljivost, kao i različiti alati koji se koriste za procenu ekološke prihvatljivosti. Pored toga, predstavljen je novi koncept bele analitičke hemije

Revealing Retention Mechanisms in Liquid Chromatography: QSRR Approach

One-factor-at-a-time experimentation was used for a long time as gold-standard optimization for liquid chromatographic (LC) method development. This approach has two downsides as it requires a needlessly great number of experimental runs and it is unable to identify possible factor interactions. At the end of the last century, however, this problem could be solved with the introduction of new chemometric strategies. This chapter aims at presenting quantitative structure–retention relationship (QSRR) models with structuring possibilities, from the point of feature selection through various machine learning algorithms that can be used in model building, for internal and external validation of the proposed models. The presented strategies of QSRR model can be a good starting point for analysts to use and adopt them as a good practice for their applications. QSRR models can be used in predicting the retention behavior of compounds, to point out the molecular features governing the retention, and consequently to gain insight into the retention mechanisms. In terms of these applications, special attention was drawn to modified chromatographic systems, characterized by mobile or stationary phase modifications. Although chromatographic methods are applied in a wide variety of fields, the greatest attention has been devoted to the analysis of pharmaceuticals

Primena eksperimentalnog dizajna za razdvajanje lekova HPLC metodom

Design of Experiments (DoE) is an indispensable tool in contemporary drug analysis as it simultaneously balances a number of chromatographic parameters to ensure optimal separation in High Pressure Liquid Chromatography (HPLC). This manuscript briefly outlines the theoretical background of the DoE and provides step-by-step instruction for its implementation in HPLC pharmaceutical practice. It particularly discusses the classification of various design types and their possibilities to rationalize the different stages of HPLC method development workflow, such as the selection of the most influential factors, factors optimization and assessment of the method robustness. Additionally, the application of the DoE-based Analytical Quality by Design (AQbD) concept in the LC method development has been summarized. Recent achievements in the use of DoE in the development of stability-indicating LC and hyphenated LC-MS methods have also been briefly reported. Performing of Quantitative structure retention relationship (QSRR) study enhanced with DoE-based data collection was recomended as a future perspective in description of retention in HPLC system.Dizajn eksperimenata (DoE) je nezaobilazan alat u savremenoj analizi lekova budući da istovremeno balansira niz hromatografskih parametara kako bi se osiguralo optimalno razdvajanje u tečnoj hromatografiji pod visokim pritiskom (HPLC). Prikazana je teorijska osnova DOE i data su detaljna uputstva za njegovu primenu u HPLC ispitivanjima u farmaciji. Naročito se govori o klasifikaciji brojnih tipova dizajna i njihovim mogućnostima za racionalizaciju različitih faza tokom procesa razvoja HPLC metode, kao što su izbor najuticajnijih faktora, optimizacija faktora i procena robusnosti metode. Dodatno, sumirana je primena DOE kao sastavnog dela koncepta ugradnje kvaliteta u proizvod u domenu razvoja analitičkih metoda (AQbD) zasnovanih na HPLC tehnici. Takođe su prikazana i nedavna dostignuća u primeni DOE u razvoju LC metoda koje su pogodne za ispitivanje stabilnosti lekova, kao i LC-MS metoda. U budućoj perspektivi, preporučeno je izvođenje ispitivanja kvantitativnog odnosa između strukture i retencionog ponašanja (QSRR) analita u HPLC sistemu na osnovu podataka dobijenih primenom DOE

266 Koncept ekološki prihvatljivih hromatografskih metoda: Studija slučaja na primeru razdvajanja dronedaron hidrohlorida i njegovih degradacionih proizvoda

Recently, concern about the environmental impact of drug analysis methods has increased significantly. Reversed-phase high-performance liquid chromatography (RP-HPLC), the predominant technique in drug analysis, relies heavily on organic solvents such as acetonitrile, which is known for its chromatographic efficiency, but also for its toxicity and flammability. To address these concerns, it is essential to minimize the use of toxic organic solvents. The aim of this study is to explore greener RP-HPLC modifications and evaluate their applicability in the pharmaceutical industry. Methods were developed for the separation of dronedarone hydrochloride and its degradation products based on experimental design, including micellar liquid chromatography (MLC), β-cyclodextrin (CD) modified RP-HPLC and ultra-high performance liquid chromatography (UHPLC). The eco-friendliness of these methods was assessed using the analytical eco-scale score, green analytical procedure index (GAPI) and analytical greenness (AGREE). AGREE appears to be the most suitable, as it revealed the greatest differences between the compared methods, as well as insights into critical aspects of the methods. UHPLC and β-CD modified RP-HPLC have been shown to be superior to MLC, and both methods can be a good choice, depending on whether the ease of implementation or energy efficiency is considered to be a more important criterion.U poslednje vreme, zabrinutost za negativan uticaj metoda koje se koriste u analitici lekova na životnu sredinu je u značajnom porastu. Reverzno-fazna tečna hromatografija visokih performansi (RP-HPLC) kao dominantno korišćena tehnika u velikoj meri se oslanja na primenu organskih rastvarača, poput acetonitrila, koji je poznat po hromatografskoj efikasnosti, ali i po toksičnosti i zapaljivosti. Kako bi se ovi problemi rešili i zaštitilo zdravlje ljudi i životna sredina, neophodno je upotrebu toksičnih organskih rastvarača svesti na minimum. Cilj ovog istraživanja bio je da preporuči „zelenije“ modifikacije RP-HPLC metoda. Primenom eksperimentalnog dizajna razvijene su metode za razdvajanje dronedaron-hidrohlorida i njegovih degradacionih proizvoda, uključujući micelarnu tečnu hromatografiju (MLC), RP-HPLC metodu modifikovanu β-ciklodekstrinom (CD) i tečnu hromatografiju ultra visokih performansi (UHPLC). Ekološka prihvatljivost ovih metoda je procenjena korišćenjem analitičke eko-skale, indeksa zelene analitičke procedure (GAPI) i pristupa analitičke zelenosti (AGREE). AGREE se izdvojio kao najpogodniji, jer je pokazao najveće razlike između navedenih metoda, kao i uvid u kritične aspekte metoda. UHPLC i β-CD modifikovana RP-HPLC metoda su se pokazale superiornim u odnosu na MLC. Koja metoda će biti metoda izbora zavisi od toga da li se lakoća implementacije ili energetska efikasnost smatraju važnijim kriterijumom