abstract: This study investigates the effectiveness of the use of Concept-Based Instruction (CBI) to facilitate the acquisition of Spanish mood distinctions by second semester second language learners of Spanish. The study focuses on the development of Spanish mood choice and the types of explanations (Rule-of-Thumb vs. Concept-based) used by five students before and after being exposed to Concept-Based Instruction regarding the choice of Spanish mood following various modalities .The students in this study were presented with a pedagogical treatment on Spanish mood choice that included general theoretical concepts based on Gal'perin's (1969, 1992) didactic models and acts of verbalization, which form part of a Concept-Based pedagogical approach. In order to ascertain the effectiveness of the use of concept-based tools to promote the ability to use Spanish mood appropriately over time, a pre and post-test was administered to the group in which students were asked to respond to prompts containing modalities that elicit the indicative and subjunctive moods, indicate their level of confidence in their response, and verbalize in writing a reason for their choice. The development of these abilities in learners exposed to CBI was assessed by comparing pre and post-test scores examining both forms and explanations for the indicative and subjunctive modality prompts given. Results showed that students continued to rely on Rule-of-Thumb explanations of mood choice but they did expand their use of conceptually-based reasoning. Although the quantitative and qualitative analyses of the results indicate that most students did improve their ability to make appropriate mood choices (forms and explanations) after the CBI treatment, the increased use of conceptually-based explanations for their mood choices led to both correct and incorrect responses. / Dissertation/Thesis / M.A. Applied Linguistics 2013

The objective of this dissertation is to test some major theories on the discourse function of the Greek indicative verb-forms in narrative. Since the publication of Stanley Porter and Buist Fanning’s doctoral dissertations, verbal aspect has been a major area of research among scholars. Although the debate and research concerning the aspect of Greek verbs continues to be at the forefront of Greek grammatical studies, the question that begs to be answered is whether their answers can satisfactorily account for the varied verb-forms throughout the entirety of a historical narrative. This dissertation seeks to answer this question by testing current proposals on the discourse function of Greek indicative verb-forms within the narrative of Judith. Chapter 1 introduces the thesis of the dissertation, surveys the literature related to Greek grammar, and discusses the need to focus on discourse grammar. Chapter 2 surveys the literature related to discourse grammar, provides a methodology, and discusses the rationale for the selection of the book of Judith. Chapter 3 tests the function of the aorist and the imperfect within the book of Judith. Specifically, it tests the proposal—unless intentionally marked, the aorist is used to describe mainline events, it provides the foundation for the narrative, and thus moves it forward. Whereas the imperfect is used with non-events, giving descriptive or background information, rather than moving it forward. Chapter 4 examines the function of the present within the narrative of Judith. Namely, it evaluates Runge’s rejection of Stanley Porter’s claim that the present indicative verb-form is semantically marked for prominence. Chapter 5 observes the function of the perfect within the narrative of Judith. Specifically, it evaluates the thesis—the perfect is used to show the relevance of the action, idea, or situation to the current discourse. Chapter 6 provides a concluding summary of each chapter in this dissertation and suggests areas for fruitful future research.

M.A. / The traditional approach regarding the demonstrative in Northern Sotho, in several instances, is only partially correct.This approach is primarily concerned with the morphology of the demonstrative, whilst the semantic and syntactic elements thereof are only briefly and superficially attended to ...

The goal of this dissertation is to formulate a novel characterization of subjunctive complements in Spanish, based on semantico-pragmatic and syntactic evidence. The analysis is informed by, and has consequences for, theories that the pragmatic and semantic components of the grammar interface with the syntax. Thus, the proposal carries implications for the interpretive components of the grammar at the C-I interface. I argue that the indicative mood, in Romance, corresponds to propositions which carry assertive force. Data from Greek and Bulgarian provide evidence for a syntactic representation of this feature. I provide evidence for a novel tripartite classification of subjunctive clauses: (i) those that are lexically-selected by volitional verbs and carry strongly intensional semantics, (ii) those licensed by a non-veridical operator (i.e. negation) and carry anti-veridical semantics and (iii) those which lack illocutionary force, with the subjunctive mood surfacing as the default (uninformative) mood in complements to emotives and negated epistemics. Complements to emotive and negated epistemic predicates are the only subjunctive complements which may be extensionally anchored (to the real world), yet are incompatible with ‘point of view’ phenomena, which is unexpected in extensional contexts. The data indicate that the subjunctive surfaces in uninformative contexts, in the absence of (intensional or assertive) illocutionary force. The observations lead to a novel syntactic analysis, relying on Speas and Tenny’s (2003) representation of pragmatic arguments, which captures the fact that subjunctive clauses are anchored to a particular individual (either the matrix subject or the speaker). I propose that subject obviation occurs only in deontic and causative contexts, a novel hypothesis supported by data which illustrate that the addition of an evaluative component (an epistemic ordering source) renders subject obviation violable. I argue that a feature-checking relationship between the subordinate Seat of Knowledge position and matrix deontic or causative v anchors the complement proposition to the matrix subject’s model of evaluation. Co-reference is then banned due to a semantico-pragmatic parameter setting in Romance which disallows a de se (self-ascribing) reading in finite contexts, which facilitates the processing of pronominal reference. I argue that the semantico-pragmatic status of subjunctive complements to negated epistemic predicates overlaps with those to both emotives, which are evaluative, and those to other negated predicates (i.e. perception verbs, verbs of reported speech), which are evidential. Their dual status accounts for the (previously unobserved) overlapping syntactic and semantic properties exhibited in their subjunctive complements. Partee’s (1991, 1995) proposal for a tripartite structure of negation elegantly captures the interpretive facts. Subjunctive complements to negated evidential predicates are interpreted in the scope of negation, while those to evaluative (emotive) predicates are interpreted in the restrictor, with those to negated epistemics allowing both options. Two different types of negation are identified, following Horn’s (1989) analysis. The pragmatic classification of the predicate as either evidential or evaluative determines the type of negation with which it may surface. Metalinguistic negation surfaces with evaluative predicates, and does not scope into the complement clause. True negation-triggered subjunctive (i.e. evidential contexts) results from the scope of descriptive negation into the complement clause, which carries a negative clause-type feature. I show that negation-triggered subjunctive clauses constitute unbounded events, which is attributed to their anti-veridical status. In conclusion, the analysis characterizes subjunctive clauses in Spanish, and carries implications for cross-linguistic analysis. More research is needed to verify the claims cross-linguistically, and the analysis lacks a precise characterization of indicative complement clauses which, like subjunctive clauses, require a more fine-grained characterization.

Made available in DSpace on 2016-04-28T19:34:01Z (GMT). No. of bitstreams: 1 Alice Felicissimo.pdf: 1703689 bytes, checksum: 8770a1a675553f8f6cd3dbddfdca9e92 (MD5) Previous issue date: 2015-09-16 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This paper describes the occurrences of the Subjunctive Mode with the notion of futurity, to express the not factual and the variation of the present subjunctive mode by use of the present Indicative Mode. The research is based on principles of linguistic functionalism and has as a starting point the grammatical rules of the normative standard proposed by Brazilian traditional grammarians. The use of Subjunctive Mode, as the variation, was studied from the perspective of the emergent grammar of Givón, focused on grammar for communication and that emerges from communicative purposes shaping the discourse. We considered as a dependent variable of verbal mode, for understanding the phenomenon of alternation between subjunctive and indicative mode, the linguistic aspects: type of clause, verbal choice of main clause and verbal tense of the occurrence (the subordinate clause or independent clause). The sememe of futurity, identified in the propositional level, tends to preserve the use of the subjunctive mode, according to the normative standard grammar, and is used by speakers of medium and high level of education. For the use of the Indicative Mode with the imperative function, we found out that the selection of verbal morphology is under pressure of pragmatic-discursive relationship. The Indicative Mode serves to express the Imperative Mode, not containing the "order". This usage occurs in Brazilian Portuguese with speakers of all levels of education in face-to-face situations and with proximity. In subordinate clauses the modality of certainty of who speaks, even if it refers to future tense, propitiates the use of the Indicative Mode. This variation also occurs with speakers of all levels of education / Este trabalho apresenta a descrição das ocorrências do Modo Subjuntivo com a noção de futuridade, de forma a expressar o não factual e a variação do Presente do Modo Subjuntivo pelo uso do Presente do Modo Indicativo. A pesquisa está fundamentada em princípios do funcionalismo linguístico e tem por ponto de partida as regras gramaticais de padrão normativo proposto por gramáticos tradicionais brasileiros. O uso do Modo Subjuntivo, assim como a variação, foi estudado numa perspectiva da gramática emergente givoniana, centrada na gramática para a comunicação, que emerge dos propósitos comunicativos moldando o discurso. Consideramos como variável dependente do modo verbal, para o entendimento do fenômeno de alternância entre os modos subjuntivo e indicativo, os aspectos linguísticos: tipo de oração, a escolha verbal da oração matriz e tempo verbal da ocorrência (na oração subordinada ou na independente). O sema de futuridade, identificado no nível proposicional, tende a preservar o uso do MS, segundo o padrão gramatical normativo, e é usado por falantes de média e alta escolaridade. Para o uso do Modo Indicativo com função de Imperativo constatamos que a seleção da morfologia verbal sofre pressão da relação pragmático-discursiva. O Modo Indicativo tem a função de expressar o Modo Imperativo, não contendo a ordem . Esse uso no Português Brasileiro ocorre com falantes de todos os níveis de escolaridade em situação presencial e de proximidade. Nas orações subordinadas a modalidade da certeza de quem fala, ainda que ela remeta ao tempo futuro, propicia o uso do Modo Indicativo. Essa variação ocorre, também, com falantes de todos os níveis de escolaridade

in English Expression of Posteriority in Spanish through Indicative and Subjunctive The aim of this thesis is to study those paradigms in indicative and subjunctive which express the absolute and relative posteriority in Spanish. Our thesis is based on the literature related with the topic and also on the language corpora. We study the particular paradigms, their contexts and the possibilities of their mutual alternation. A considerable part of the thesis is dedicated to the absolute posteriority. We study the paradigms in indicative not only with respect to the time delimitation but also in term of the context and attitude of the speaker. As for the paradigms in subjunctive, we focus on the types of subordinate clauses. In the chapter dedicated to the relative posteriority, we demonstrate which paradigms correspond to the paradigms in absolute posteriority. We briefly compare the situation in Spanish with the one in Czech. Based on the results of our case studies and information from literature, we came to the conclusion that it is not possible to simply classify the particular uses of the paradigms and that is important to take several factors into consideration, not only the distance of action from the moment of speech.

Com base nos pressupostos teórico-metodológicos da Sociolinguística Variacionista (LABOV, 2008 [1972]; 2001), esta pesquisa investiga o emprego de formas verbais subjuntivas e indicativas em três contextos de subordinação orações adverbiais, substantivas (na posição de complemento do verbo da oração principal) e relativas. Os dados foram extraídos de 36 entrevistas sociolinguísticas com paulistanos e 36 entrevistas com ludovicenses, estratificadas de acordo com o sexo/gênero dos informantes, sua faixa etária (18 a 35; 36 a 59; e 60 anos ou mais) e seu nível de escolaridade (médio superior). Examinam-se as variáveis linguísticas e sociais que se correlacionam à ocorrência dessas formas. Entre as linguísticas, incluem-se variáveis como o tempo verbal da oração subordinada; o tipo de subordinador (tais como se e embora, no caso das orações adverbiais); o verbo da oração principal e o tempo verbal da oração principal (no caso das orações substantivas). Propõe-se que, em português, formas subjuntivas e indicativas funcionam como variantes de uma variável apenas nas orações adverbiais, ao passo que, nos outros dois contextos, tais formas se alternam mas não constituem sempre formas de dizer a mesma coisa (LABOV, 1972; 1978). A análise quantitativa dos dados foi feita com o pacote estatístico GoldVarb X (SANKOFF, TAGLIAMONTE, SMITH, 2005). Os resultados indicam que, no geral, é maior a tendência de ocorrência do modo indicativo em São Paulo relativamente a São Luís. Por outro lado, há indício de mudança na fala ludovicense, na direção do indicativo, em orações adverbiais e substantivas. / Based on the theory and methods of Variationist Sociolinguistics (LABOV, 2008 [1972]; 2001), this master thesis investigates the use of indicative and subjunctive verbal forms in three contexts of subordination: adverbial, nominal and relative clauses. The data were extracted from 36 sociolinguistic interviews with native speakers from São Paulo and 36 from São Luís, stratified by sex/gender, age (18-35 years old, 36 to 59, and 60 or older) and level of education (high school or college). Social and linguistic independent variables are examined vis-à-vis their correlation to the occurrence of those forms. Among the linguistic factors are the verbal tense in the subordinate clause, the subordinator (as se if and embora though, for adverbial clauses), the verb and the verb tense in the main clause (for the nominal clauses, embedded in the position of the verbal complement). This thesis discusses that, in Brazilian Portuguese, subjunctive and indicative forms function as variants of a variable in adverbial clauses, but not in nominal or relative clauses, in which they are not different ways of saying the same thing (Labov, 1972; 1978). The quantitative analyses were developed on GoldVarb X (SANKOFF, TAGLIAMONTE, SMITH, 2005). The results suggest that indicative forms tend to occur more in São Paulo relatively to São Luís. However, theres change in progress in São Luís (apparent time), with the indicative being favored by younger speakers, both in adverbial and nominal subordinate clauses.

Orientador: Gladis Massini-Cagliari / Banca: Luiz Carlos da Silva Schwindt / Banca: Beatriz Nunes de Oliveira Longo / Resumo: Este estudo tem como objetivo principal fazer um vínculo entre o passado e o presente, comparando processos morfofonológicos desencadeados pela flexão verbal através das formas do pretérito perfeito do modo indicativo, ou seja, processos que alteram a forma dos morfemas e geram alomorfias em vários níveis no Português Arcaico (PA) dos séculos XII-XIII analisados a partir de teorias não lineares (cf. Fonologia Lexical, Fonologia métrica e Geometria de Traços). Para a realização desta pesquisa foram considerados como objeto as formas verbais do pretérito perfeito do modo indicativo, tanto dos verbos regulares quanto dos verbos irregulares. A metodologia foi baseada no mapeamento das formas verbais nas Cantigas de Santa Maria. Contamos também com glossários, vocabulários, dicionários, e especialmente o glossário de Mettmann (1972), como auxílio na categorização das formas verbais. Depois de coletados, os dados foram separados de acordo com o tipo de processo morfofonológico verificado. O corpus de base, para o PA, foi constituído pelas Cantigas de Santa Maria (CSM), elaboradas em galego-português e atribuídas a Dom Afonso X de Castela, o Sábio, com a colaboração de trovadores, músicos, desenhistas e miniaturistas que acolhia em sua corte. Correspondem a um monumento literário de mais elaborada importância, que ocupa um lugar privilegiado na literatura medieval galego-portuguesa. Ao final da análise dos processos morfofonológicos, nos resultados obtidos, verificamos a alta produtividade da harmonização vocálica e da neutralização e crase da vogal temática em um estágio inicial da língua que denominamos de período arcaico. Podemos comprovar que os processos morfofonológicos, sobretudo a harmonia vocálica, já ocorriam desde o estágio inicial do português com as mesmas características e produtividade dos dias de hoje, uma vez que, na passagem do latim... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: This study aims to make a link between past and present, comparing morphophonological processes triggered by verbal inflection through the forms of the past tense of the indicative, that is, processes that alter the shape of morphemes and generate allomorphs at various levels in the Archaic Portuguese (AP) of XII-XIII centuries were investigated by Lexical Phonology (LP) and Autosegmental and Metrical Phonology. The past tense verb forms of the indicative mood both of regular and irregular verbs were considered as an object for this research. The methodology was based on the mapping of verb forms in the Cantigas de Santa Maria (CSM). We have also used glossaries, vocabularies, dictionaries, and especially the glossary of Mettmann (1972) as an aid in the categorization of verbal forms. Once collected, the data was separated according to the type of morphophonogical process checked. The corpus was formed by the Cantigas de Santa Maria (CSM), written in Galician-Portuguese and attributed to Don Alfonso X of Castile, the Wise, in collaboration with the troubadours, musicians, designers and miniaturists who lived in his court. The CSM correspond to the most elaborate literary monument, which occupies a privileged place in the medieval Galician-Portuguese literature. After the analysis of the morphophonological processes, in the results obtained, we verified the high productivity of vowel harmony and vowel neutralization and at an early stage of the language that corresponds to the archaic period. We could prove that the morphophonological processes, especially vowel harmony, have occurred since the initial stage of the Portuguese with the same characteristics and productivity of today, since in the passage from Latin to Portuguese, the verb conjugations were already well defined. In addition to the morphophonological processes, we also mapped the irregular verbs that we called... (Complete abstract click electronic access below) / Mestre

Com base nos pressupostos teórico-metodológicos da Sociolinguística Variacionista (LABOV, 2008 [1972]; 2001), esta pesquisa investiga o emprego de formas verbais subjuntivas e indicativas em três contextos de subordinação orações adverbiais, substantivas (na posição de complemento do verbo da oração principal) e relativas. Os dados foram extraídos de 36 entrevistas sociolinguísticas com paulistanos e 36 entrevistas com ludovicenses, estratificadas de acordo com o sexo/gênero dos informantes, sua faixa etária (18 a 35; 36 a 59; e 60 anos ou mais) e seu nível de escolaridade (médio superior). Examinam-se as variáveis linguísticas e sociais que se correlacionam à ocorrência dessas formas. Entre as linguísticas, incluem-se variáveis como o tempo verbal da oração subordinada; o tipo de subordinador (tais como se e embora, no caso das orações adverbiais); o verbo da oração principal e o tempo verbal da oração principal (no caso das orações substantivas). Propõe-se que, em português, formas subjuntivas e indicativas funcionam como variantes de uma variável apenas nas orações adverbiais, ao passo que, nos outros dois contextos, tais formas se alternam mas não constituem sempre formas de dizer a mesma coisa (LABOV, 1972; 1978). A análise quantitativa dos dados foi feita com o pacote estatístico GoldVarb X (SANKOFF, TAGLIAMONTE, SMITH, 2005). Os resultados indicam que, no geral, é maior a tendência de ocorrência do modo indicativo em São Paulo relativamente a São Luís. Por outro lado, há indício de mudança na fala ludovicense, na direção do indicativo, em orações adverbiais e substantivas. / Based on the theory and methods of Variationist Sociolinguistics (LABOV, 2008 [1972]; 2001), this master thesis investigates the use of indicative and subjunctive verbal forms in three contexts of subordination: adverbial, nominal and relative clauses. The data were extracted from 36 sociolinguistic interviews with native speakers from São Paulo and 36 from São Luís, stratified by sex/gender, age (18-35 years old, 36 to 59, and 60 or older) and level of education (high school or college). Social and linguistic independent variables are examined vis-à-vis their correlation to the occurrence of those forms. Among the linguistic factors are the verbal tense in the subordinate clause, the subordinator (as se if and embora though, for adverbial clauses), the verb and the verb tense in the main clause (for the nominal clauses, embedded in the position of the verbal complement). This thesis discusses that, in Brazilian Portuguese, subjunctive and indicative forms function as variants of a variable in adverbial clauses, but not in nominal or relative clauses, in which they are not different ways of saying the same thing (Labov, 1972; 1978). The quantitative analyses were developed on GoldVarb X (SANKOFF, TAGLIAMONTE, SMITH, 2005). The results suggest that indicative forms tend to occur more in São Paulo relatively to São Luís. However, theres change in progress in São Luís (apparent time), with the indicative being favored by younger speakers, both in adverbial and nominal subordinate clauses.

Submitted by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-09-22T20:18:29Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) RAQUEL BALESTRI HELENO FERREIRA ate AGO 2021.pdf: 1629744 bytes, checksum: 7d6690d50c0536d3f7683a73db84827d (MD5) / Approved for entry into archive by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-09-22T20:18:45Z (GMT) No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) RAQUEL BALESTRI HELENO FERREIRA ate AGO 2021.pdf: 1629744 bytes, checksum: 7d6690d50c0536d3f7683a73db84827d (MD5) / Made available in DSpace on 2016-09-22T20:18:45Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) RAQUEL BALESTRI HELENO FERREIRA ate AGO 2021.pdf: 1629744 bytes, checksum: 7d6690d50c0536d3f7683a73db84827d (MD5) Previous issue date: 2016 / A linagliptina (LGT) é um fármaco inibidor da DPP-4, da classe das gliptinas, utilizado para o controle glicêmico de diabetes mellitus tipo 2. Levando-se em conta que os fármacos utilizados no processo de produção das formulações farmacêuticas não são considerados totalmente puros, alguns Guias Regulatórios (ICH) descrevem a necessidade da quantificação do fármaco e suas impurezas de síntese. Diante disso, o objetivo do estudo é o desenvolvimento de um método por cromatografia líquida de alta eficiência (CLAE) para quantificação do fármaco e de suas três principais impurezas de síntese e o estudo de segurança biológica destas substâncias. O desenvolvimento e a validação do método para LGT e das três impurezas foram realizados por CLAE acoplada a um detector de arranjo de diodo (DAD), utilizando coluna C8 (5 μm - 4,6x100 mm), fase móvel eluída em modo gradiente, constituída de uma mistura de ácido fórmico 0,1% pH 3,5 e acetonitrila (ACN) eluída com uma rampa crescente de 10% na proporção de ACN de (0) zero ao 4 min (30% para 70%) e decrescente de 10% na proporção de ACN de 5 a 8 min (70% para 30%), vazão de 0,6 mL/min, volume de injeção de 20 μL e temperatura do forno de 30°C. Os comprimentos de onda de detecção utilizados foram 294, 278, 268 e 280 nm para LGT, impureza 1, 2 e 3, respectivamente. O método apresentou-se seletivo e específico para a LGT e as impurezas, pois não houve interferência dos produtos de degradação por Ultravioleta A, hidrólise básica (hidróxido de sódio 1,0 mol/L) e ácida (ácido clorídrico 1,0 mol/L), peróxido hidrogênio 30%, temperatura 60 °C e hidrólise básica e ácida em condições térmicas à 80 °C e dos excipientes na quantificação do fármaco. A resposta foi linear na faixa de 2,41-144,0 μg/mL (r = 0,9996) para a LGT e na faixa de 0,06-3,6 μg/mL para as impurezas testadas (r = 0,9963, 0,9994 e 0,9991 para impureza 1, 2 e 3, respectivamente). O método demonstrou exatidão, com teores de recuperação de 99,79, 93,12, 92,92 e 93,99% para a LGT e impureza 1, 2 e 3, respectivamente. A precisão intra e inter-dia foi satisfatória (RSD 1,36, 4,14, 3,50 e 4,08% para a LGT e impureza 1, 2 e 3, respectivamente) e a robustez não apresentou diferenças significativas com pequenas alterações nas condições analíticas (pH, fase móvel, temperatura, fluxo e detector). A cinética de degradação em condição alcalina associada a temperatura de (80 ºC), apresentou resultados de primeira ordem. A avaliação da segurança biológica foi realizada por meio da citotoxicidade, mutagenicidade e genotoxicidade através dos testes de viabilidade celular, micronúcleo e cometa, respectivamente. Nos testes de segurança biológica a LGT apresentou-se apenas citotóxica na concentração 10 vezes superior a concentração plasmática máxima, enquanto as impurezas 1 e 3 apresentaram-se citotóxica, mutagênica e genotóxica em uma concentração equivalente a 10% concentração plasmática máxima do fármaco e a impureza 2 evidenciou sua citotoxicidade e genotoxicidade na concentração equivalente a 10% da concentração plasmática máxima do fármaco. De acordo com os resultados obtidos, pode-se observar que o método proposto foi indicativo de estabilidade por CLAE para LGT e ainda demonstrou-se adequado para análise quantitativa das impurezas de síntese do fármaco. Além disso, evidenciou-se que a LGT e as impurezas de síntese estão em conformidade com os testes de segurança biológica empregados, desde que utilizadas nas concentrações adequadas. / Linagliptin (LGT) is an inhibitor of DPP4 used for glycemic control of type 2 mellitus diabetes. Since the drugs used in the production process of the pharmaceutical formulations are not considered totally pure, the Regulatory Guides describing the need of the drug quantification and impurities potentials. Therefore, the aim of this study was to develop a method by highperformance liquid chromatography to quantify the drug and three potential synthetic impurities and biological safety studies. The development and validation of the method for LGT and the three impurities were carried out by HPLC coupled to a photodiode array detector. The chromatographic separation was performed in a RP8 column (150 x 4.6 mm, 5 μm), at 30°C. The separation was performed by means of a linear gradient elution (eluent A: formic acid 0.1% pH 3.5; eluent B: acetonitrile). The gradient obeys the following sequence: 3070% of B (0 - 4 minutes) and 7030 of B (4,01 - 8 minutes) at a flowrate of 0.6 mL min1 and run time of 10 minutes. The injection volume was 20 μL and detection at 294, 278, 268 e 280 nm for LGT, impurity 1, 2 and 3, respectively. The method showed selectivity and specific for the LGT and synthetic impurities, therefore no interference of degradation products (UV-A, basic hydrolysis (sodium hydroxide 1.0 mol L1) and acid (hydrochloric acid 1.0 mol L1), peroxide (30%), temperature (60 ° C) and acidic and basic hydrolysis under thermal conditions (80° C)) and the excipients in the quantification of the drug. The response was linear from 2.41 to 144.0 μg mL1 (r = 0.9996) for the LGT and in the range of 0.06 to 3.6 μg mL1 (r = 0.9963, 0.9994 and 0.9991 for impurity 1, 2 and 3, respectively ). The method showed accuracy, with recovery levels of 99.79, 93.12, 92.92 and 93.99% for LGT and impurity 1, 2 and 3, respectively. The intra and inter-day precision was suitable (RSD 1.36, 4.14, 3.50 and 4.08% for LGT and impurity 1, 2 and 3, respectively) and the robustness showed no significant differences with small changes in the analytical conditions (pH of the mobile phase, temperature, flow-rate and detector). The kinetics of degradation in alkaline conditions associated with temperature (80° C), showed results of the first order. The evaluation of the biological was performed by cytotoxicity, mutagenicity and genotoxicity through the cell viability test, micronucleus and comet, respectively. In biological safety testing LGT had only cytotoxic activity at a concentration of 10 times the maximum plasma concentration, while the impurity 1 and 3 set out cytotoxic, mutagenic and genotoxic in a concentration equivalent to 10% maximum plasma concentration of the drug and impurity 2 showed cytotoxicity and genotoxicity in concentration equivalent to 10% of the maximum plasma concentration of the drug. According to the results, it can be seen that the proposed method by HPLC is stability-indicating and suitable for quantitative analysis of the drug and synthetic impurities. Furthermore, it was observed that the LGT and synthetic impurities are in accordance with biological safety studies, if they are used in appropriate concentration.