Validation of qualitative analytical methods

VALIDACIO DE METODES DANALISIS QUALITATIVA La informacio quimica sobre la composicio duna mostra pot ser molt diversa: des de saber de quins analits es composa un cert material a saber exactament en quina quantitat shi troben o de quina forma hi son presents, si estan relacionats estructuralment entre ells, etc. Dacord amb tota aquesta varietat, els metodes analitics es classifiquen en dos grans grups: els metodes danalisi qualitativa i els metodes danalisi quantitativa. Segons les caracteristiques del problema analitic es triara un o altre tipus de metode danalisi. Quan lobjectiu es saber que hi ha en una mostra desconeguda, un metode qualitatiu sera el mes adequat. En els darrers temps, aquests metodes han estat objecte destudi, i sutilitzen avui dia, en molts camps daplicacio. Per exemple, en lanalisi daliments es habitual lus dun metode qualitatiu per determinar si un o mes analits es troben presents en la mostra per sobre o per sota duna determinada concentracio. Pero si linteres es saber la quantitat dun determinat component en una mostra, lopcio dun metode quantitatiu sera la mes adient. Aquesta tesi sha centrat en els metodes danalisi qualitativa pels nombrosos avantatges que presenten. Aquests metodes poden ajudar a destriar mostres en funcio de si aquestes presenten una quantitat dun cert analit al voltant dun valor de concentracio previament establert, abans de ser quantificades. Es a dir, sutilitzen com a pas previ a laplicacio del metode quantitatiu, implicant un estalvi de feina, de temps i de diners important si es tracta de quantificar contaminants, detectar adulteracions o qualsevol altra situacio en la que no es pugui sobrepassar una certa concentracio. En aquests casos nomes sha de quantificar la mostra que en el metode qualitatiu revela un resultat en el que es sobrepassa aquesta certa concentracio. En daltres ambits daplicacio, els metodes qualitatius estan perfectament integrats en el procediment estandard doperacions, pel que, llevat en situacions molt especifiques, un resultat positiu no necessita ser confirmat mitjancant una analisi posterior amb un metode quantitatiu. A mes de la importancia de triar un metode analitic adequat a cada problematica, cal destacar que es igual dimportant tenir fiabilitat sobre el resultat trobat i, per tant, sobre el metode emprat. Aixo vol dir que qualsevol metode analitic ha de tenir definits els seus requeriments i qualitats analitiques i que sha de comprovar que aquests parametres previament definits, realment tenen el valor que sels ha assignat. Daquesta confirmacio sen diu Validacio, i es una condicio indispensable per a poder emprar un metode analitic. Daquesta manera es poden garantir els resultats demanats pels clients/usuaris. A mes, des de laprovacio de la norma ISO 17025 aquesta comprovacio del metode analitic i dels seus resultats encara sha fet mes recomanable. Fins fa poc temps, la validacio de metodes analitics sha centrat en els metodes quantitatius. El resultat ha estat una serie de guies/pautes perfectament establertes dus molt comu. Pero no hi ha cap protocol general per a validar un metode qualitatiu. Amb aquesta tesi es vol contribuir a millorar aquesta situacio. Es comenca amb una revisio de les classificacions i de les definicions lligades a aquests metodes, a mes dun repas sobre quines institucions han fet esment daquest tema. Es segueix amb una proposta de classificacio daquests metodes i, finalment, es defineixen aquells parametres de qualitat que es consideren mes importants en la validacio. En les tres aplicacions practiques presentades es descriuen les caracteristiques intrinseques del metode danalisi qualitativa. Despres, es defineixen els parametres que sadequen millor als requeriments del metode i, finalment, es proposa un protocol de validacio que permet el seu establiment. El cas de la revisio de les classificacions i definicions emprades en aquest ambit, com en el cas de la presentacio de les contribucions corresponents a diferents institucions, shan traduit en dues publicacions que sadjunten en la tesi. Pel que fa a les aplicacions practiques, una delles tambe sinclou com a article publicat i les altres dues, sinclouen com a articles acceptats VALIDATION OF QUALITATIVE ANALYTICAL METHODS The chemical information about the composition of a sample can be of different nature: which species are in the sample, their concentration or if they are structurally related, etc. In order to fit any of these requirements, either a qualitative or a quantitative analytical method may be used. If the aim is to identify species, a qualitative method will suit the problem at hand. These types of methods have been recently studied and nowadays are being increasingly used in several fields of analysis. For example, it is common to use qualitative methods as far as food analysis is concerned. On the contrary, if the aim is to quantify one or more analytes of a sample, a quantitative method will be very useful. This thesis has focused on qualitative analytical methods because they provide several advantages and they are being increasingly used. These types of methods can screen samples according to the presence or absence of certain analytes with regard to a pre-set level of concentration. That is to say, they are used as a step before the quantitative method and results in lower analysis time and costs because analyte quantification is not required in all situations. There are some particular analysis fields where qualitative methods are used as routine methods. Therefore, analyte quantification is not always necessary. Moreover, it is also important to provide reliable results, that is to say, to assure that the method performs with reliability. Any analytical method must have its requirements and its analytical properties previously defined, and their values must be proven. To confirm that the requirements and the analytical properties are the right ones and to confirm that they have the right values is to validate the analytical method. This is a necessary condition to use an analytical method. In this sense, the reliability of the results given to the clients or to the users is assured. Moreover, the ISO Standard 17025 strongly encourages method validation. Method validation has focused on quantitative methods. Therefore and as a result, there are more standards or guidelines addressed to quantitative methods validation. These guidelines are commonly used by several communities of practitioners. However, there is no generally accepted standard or validation procedure addressed to qualitative methods. In this sense, this thesis aims to contribute with the development of several validation procedures. The starting point is to provide an overview as a result of a bibliographic search concerning qualitative methods validation. This overview includes the criteria existing for qualitative methods classification as well as the institutions committed the validation of these methods. After that, a classification of these methods is suggested and the most relevant performance parameters in the validation process are defined. The subsequent practical applications describe the intrinsic characteristics of the corresponding qualitative analytical method. After that, the performance parameters that best fit the requirements and the characteristics of the method are defined and, finally, a validation strategy is proposed. Bear in mind, that the strategy considers the intrinsic characteristics of the analytical method. The overview including relevant aspects such as qualitative methods classification, performance parameters definitions and the institutions committed to qualitative method validation, among others, are presented as two publications included in the thesis. Regarding the three practical applications, they are presented as three accepted papers.