Daniel Campos, as LatAm manager, has been in charge of Bioequivalence (BQV) teams in Brazil and Colômbia. He has also been dealing with innovation projects, mostly incremental innovation. He earned the Phamacy degree in 2001 at UNESP/SP and a Master degree in Toxicology in 2004 at USP/SP as well as Ph.D. in Pharmacology in 2008 at UNICAMP/SP. He has also received training in Biopharmacy and IVIVC from Drug Delivery Foundation and Instituto de Salud Publica de Chile (2004-2005). Currently, he has joined the Technical team to review the topics regarding Safety and Efficacy of the RDC 200 (Innovation).Daniel Campos was a technical consultant at ANVISA (2002-2005) and Senior Pharmacist at UNIFAG (CRO certified by ANVISA - 2005-2008). Additionally, he held the position of assistant professor of Scientific Research Methodology and Research Ethics at USF/SP (2009). Prior to leading the BQV and EQFAR teams at Medley as coordinator (since 2012), he was BQV supervisor and Regulatory expert at EMS (2008-2012). He is also co-author of books regarding PK and BQV. He is currently co-advisor for an IVIVC Thesis at USF. He is a speaker at various training courses about PK, BQV and IVIVC. Address: Brazil
Quetiapine is an atypical antipsychotic recommended as first-line treatment for acute bipolar dep... more Quetiapine is an atypical antipsychotic recommended as first-line treatment for acute bipolar depression. The extended-release quetiapine formulation is intended to be administered as an once-daily dosing. The development of an in vitro-in vivo correlation (IVIVC) and the use of in vitro data to predict in vivo bioavailability parameters has been of great interest for the rational development and evaluation process for extended release dosage forms. The aim of this study was to develop an IVIVC for quetiapine extended release formulation. In vitro dissolution rate data were obtained using USP apparatus 2 at 50 rpm, in 3 bio-relevant dissolution media with different pH values (1.2, 4.5 and 6.8). The drug release profiles of the 2 extended release dosage forms were compared using the similarity factor (f 2). The relative bioavailability of quetiapine was evaluated by a single-dose, randomized-sequence, open-label, 2 period cross over study with 16 healthy volunteers. A linear level A IVIVC model was established using percentage of absorbed and dissolved data obtained at pH 1.2. The developed IVIVC model was employed to predict quetiapine concentration-time profiles, as well as the bioequivalence parameters for test formulation. Percent prediction errors were estimated for Cmax and AUC to evaluate the validity of the correlation. The values did not exceed 15%, proving the predictability of the correlation model. In conclusion, the established level A IVIVC model proved to be an excellent tool for predicting the rate and extent of quetiapine absorption as characterized by Cmax and AUC for test formulation.
Introdução: A trazodona é um antidepressivo atípico derivado da triazolopiridina, indicado para o... more Introdução: A trazodona é um antidepressivo atípico derivado da triazolopiridina, indicado para o tratamento da depressão com ou sem episódios de ansiedade, dor associada à neuropatia diabética e outros tipos de dor crônica. Objetivo: Este estudo teve como objetivo avaliar a bioequivalência entre a formulação teste de Trazodona 100 mg (Sanofi Medley Farmacêutica Ltda) e o produto de referência, Donaren (Apsen Farmacêutica S/A) de acordo com a legislação vigente. Método: Foi realizado um estudo cruzado, aberto, randomizado, de dose única com indivíduos saudáveis de ambos os sexos. A fase clínica foi realizada com 48 indivíduos que receberam os medicamentos em condições de alimentação. A fármaco foi quantificado no plasma por cromatografia líquida acoplada a espectrometria de massas (LC-MS/MS). A avaliação da bioequivalência foi baseada em critérios de aceitação pré-definidos de 80,00 – 125,00% para o intervalo de confiança de 90% para a razão dos produtos teste e referência para os...
Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Société canadienne des sciences pharmaceutiques, 2005
A sensitive, robust, and selective liquid chromatographic-tandem mass spectrometric method (LC-MS... more A sensitive, robust, and selective liquid chromatographic-tandem mass spectrometric method (LC-MS/MS) was developed and validated for paroxetine quantification in human EDTA plasma. Sample preparation was based on liquid-liquid extraction using a mixture of ethyl acetate/hexane (50/50; v/v) to extract the drug and internal standard from plasma. Chromatography was performed on a C-18 analytical column and the retention times were 1.6 and 1.7 for paroxetine and fluoxetine (IS), respectively. The ionization was optimized using ESI(+) and selectivity was achieved by tandem mass spectrometric analysis using MRM functions, 330.0 --> 70.0 and 310 --> 43.9 for paroxetine and fluoxetine. Analytical curve ranged from 0.2 to 20.0 ng/mL. Inter-day precision and accuracy of the quality control (QC) samples were < 15% relative standard deviation (RSD). Analyte stability during sampling processing and storage were established. Validation results on linearity, specificity, accuracy, precis...
Here we present a sensitive and specific liquid chromatography-tandem mass spectrometric method f... more Here we present a sensitive and specific liquid chromatography-tandem mass spectrometric method for the quantification of dimenhydrinate (I) in human plasma. Sample preparation is conducted using citalopram (II) addition as an internal standard (IS), liquid-liquid extraction with basified plasma using a mixture hexane/acetate (1:1, v/v) as the extracting solvent, and the final extract reconstituted in the mobile phase. I and II (IS) were injected in a C8 column with the mobile phase composed of methanol:isopropanol:water:formic acid (78.00:19.92:2.00:0.08, v/v/v/v) and monitored using a positive electrospray source with tandem mass spectrometry analyses. The selected reaction monitoring (SRM) was set using precursor ion and product ion combinations of m/z 256.0&gt;167.0 and m/z 325.0&gt;109.0 for I and II, respectively. The limit of quantification (LOQ) was 0.4 ng/mL, the dynamic range being 0.4-200 ng/mL. Validation results on linearity, specificity, accuracy, precision and stability, as well as on application to the analysis of plasma samples taken up to 24 h after oral administration of 100 mg of dimenhydrinate in healthy volunteers demonstrated its applicability to bioavailability studies.
The aim of the present study was to bring additional evidence regarding a biopredictive dissoluti... more The aim of the present study was to bring additional evidence regarding a biopredictive dissolution medium containing 1% sodium lauryl sulphate (SLS) to predict the in vivo behavior of carbamazepine (CBZ) products. Twelve healthy volunteers took one immediate release (IR) dose of either test and reference formulations in a bioequivalence study (BE). Dissolution profiles were carried-out using the medium. Level A in vitro–in vivo correlations (IVIVC) were established using both one-step and two-step approaches as well as exploring the time-scaling approach to account for the differences in dissolution rate in vitro versus in vivo. A detailed step by step calculation was provided to clearly illustrate all the procedures. The results show additional evidence that the medium containing 1% SLS can be classified as a universal biopredictive dissolution tool, and that both of the approaches used to develop the IVIVC (one and two-steps) provide good in vivo predictability. Therefore, this b...
A high incidence of positive cases for cannabinoids, in analyses for doping control in sports, ha... more A high incidence of positive cases for cannabinoids, in analyses for doping control in sports, has been observed since the International Olympic Committee (IOC) included them in the 1989 list of prohibited drugs under the title of classes of prohibited substances in certain circumstances. Where the rules of sports federations so provide, tests are conducted for marijuana, hashish or any other cannabis product exposure by means of urinalysis of 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (carboxy-THC) the main metabolite of delta-9-tetrahydrocannabinol (THC). Concentrations &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;15 ng/mL (cut-off value) in confirmatory analytical procedures are considered doping. Cannabis is an illicit drug in several countries and has received much attention in the media for its potential therapeutic uses and the efforts to legalise its use. Studies have demonstrated that the use of cannabinoids can reduce anxiety, but it does not have ergogenic potential in sports activities. An increase in heart rate and blood pressure, decline of cardiac output and reduced psychomotor activity are some of the pharmacological effects of THC that will determine a decrease in athletic performance. An ergolytic activity of cannabis products has been observed in athletes of several different sport categories. In Brazil, analyses for doping control in sports, performed in our laboratories, have detected positive cases for carboxy-THC in urine samples of soccer, volleyball, cycling and other athletes. It is our intention to discuss in this article some points that may discourage individuals from using cannabis products during sports activities, even in the so-called permitted circumstances defined by the IOC and some sports federations.
The study was developed to compare the in vitro dissolution profiles of pantoprazole (CAS 102625-... more The study was developed to compare the in vitro dissolution profiles of pantoprazole (CAS 102625-70-7) formulations in both The United States Pharmacopeia (USP) apparatus 2 and 3 by applying biorelevant medium. Moreover, an in vitro-in vivo relationship was proposed considering in vivo data from a previously published study. In vitro dissolution profiles were evaluated in biorelevant medium in USP apparatus 2 and 3 and the dissolution curves were either compared by the similarity factor (f2) or a model-independent approach. The fraction of drug dissolved in vitro in apparatus 2 was compared with the fraction of drug absorbed in vivo, which was obtained from a retrospective in vivo study. An in vitro-in vivo relationship analysis was then applied to elucidate the overall absorption characteristics of formulations. The dissolution profiles of formulations demonstrated similar disposition in biorelevant medium in both USP apparatus 2 and 3. The dissolution profiles were described by f2 model in apparatus 2 and Weibull&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s function in apparatus 3. The vitro-in vivo relationship analysis showed that the formulations exhibited permeability rate-limiting absorption. Biorelevant medium in both USP apparatus 2 and 3 may be used as a tool to predict in vivo disposition of formulations of pantoprazole. Furthermore, it can be argued that biowaiver can be granted for enteric coated formulations of pantoprazole on the basis of in vitro dissolution profile.
Revista Brasileira de Ciências Farmacêuticas, 2005
ABSTRACT Esteróides androgênicos anabólicos (EAA) são substâncias naturais, sintéticas ou semi-si... more ABSTRACT Esteróides androgênicos anabólicos (EAA) são substâncias naturais, sintéticas ou semi-sintéticas derivadas da testosterona, utilizadas em atividades esportivas com o objetivo de melhorar o desempenho físico pelo aumento de massa e força muscular. Apesar de causarem efeitos tóxicos graves, principalmente sobre os sistemas cardiovascular, hepático e neuro-endócrino, os EAA têm sido amplamente utilizados no âmbito esportivo. Desta forma, o presente trabalho teve como objetivo a validação de um método para a determinação de esteróides e/ou seus produtos de biotransformação em amostras de urina por cromatografia gasosa acoplada à espectrometria de massas (CG-EM). O método baseou-se na hidrólise enzimática de esteróides conjugados, no emprego da extração líquido-líquido e na derivação do extrato para posterior análise por CG-EM, no modo de monitoramento seletivo de íons (SIM). O método validado cumpriu com os princípios de confiança necessários para a determinação de EAA em amostras de urina com a finalidade de controle de dopagem no esporte. Os limites de detecção dos esteróides analizados variaram de 0,5 a 15 ng/mL. Bons valores de precisão (intra e interensaio) também foram obtidos (CV&lt; 11%). Amostras de voluntários (n=10) que relataram uso de EAA foram submetidas ao método. Pela análise das amostras, foi verificado o uso dos principais esteróides utilizados no âmbito esportivo no Brasil.
Quetiapine is an atypical antipsychotic recommended as first-line treatment for acute bipolar dep... more Quetiapine is an atypical antipsychotic recommended as first-line treatment for acute bipolar depression. The extended-release quetiapine formulation is intended to be administered as an once-daily dosing. The development of an in vitro-in vivo correlation (IVIVC) and the use of in vitro data to predict in vivo bioavailability parameters has been of great interest for the rational development and evaluation process for extended release dosage forms. The aim of this study was to develop an IVIVC for quetiapine extended release formulation. In vitro dissolution rate data were obtained using USP apparatus 2 at 50 rpm, in 3 bio-relevant dissolution media with different pH values (1.2, 4.5 and 6.8). The drug release profiles of the 2 extended release dosage forms were compared using the similarity factor (f 2). The relative bioavailability of quetiapine was evaluated by a single-dose, randomized-sequence, open-label, 2 period cross over study with 16 healthy volunteers. A linear level A IVIVC model was established using percentage of absorbed and dissolved data obtained at pH 1.2. The developed IVIVC model was employed to predict quetiapine concentration-time profiles, as well as the bioequivalence parameters for test formulation. Percent prediction errors were estimated for Cmax and AUC to evaluate the validity of the correlation. The values did not exceed 15%, proving the predictability of the correlation model. In conclusion, the established level A IVIVC model proved to be an excellent tool for predicting the rate and extent of quetiapine absorption as characterized by Cmax and AUC for test formulation.
Introdução: A trazodona é um antidepressivo atípico derivado da triazolopiridina, indicado para o... more Introdução: A trazodona é um antidepressivo atípico derivado da triazolopiridina, indicado para o tratamento da depressão com ou sem episódios de ansiedade, dor associada à neuropatia diabética e outros tipos de dor crônica. Objetivo: Este estudo teve como objetivo avaliar a bioequivalência entre a formulação teste de Trazodona 100 mg (Sanofi Medley Farmacêutica Ltda) e o produto de referência, Donaren (Apsen Farmacêutica S/A) de acordo com a legislação vigente. Método: Foi realizado um estudo cruzado, aberto, randomizado, de dose única com indivíduos saudáveis de ambos os sexos. A fase clínica foi realizada com 48 indivíduos que receberam os medicamentos em condições de alimentação. A fármaco foi quantificado no plasma por cromatografia líquida acoplada a espectrometria de massas (LC-MS/MS). A avaliação da bioequivalência foi baseada em critérios de aceitação pré-definidos de 80,00 – 125,00% para o intervalo de confiança de 90% para a razão dos produtos teste e referência para os...
Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Société canadienne des sciences pharmaceutiques, 2005
A sensitive, robust, and selective liquid chromatographic-tandem mass spectrometric method (LC-MS... more A sensitive, robust, and selective liquid chromatographic-tandem mass spectrometric method (LC-MS/MS) was developed and validated for paroxetine quantification in human EDTA plasma. Sample preparation was based on liquid-liquid extraction using a mixture of ethyl acetate/hexane (50/50; v/v) to extract the drug and internal standard from plasma. Chromatography was performed on a C-18 analytical column and the retention times were 1.6 and 1.7 for paroxetine and fluoxetine (IS), respectively. The ionization was optimized using ESI(+) and selectivity was achieved by tandem mass spectrometric analysis using MRM functions, 330.0 --> 70.0 and 310 --> 43.9 for paroxetine and fluoxetine. Analytical curve ranged from 0.2 to 20.0 ng/mL. Inter-day precision and accuracy of the quality control (QC) samples were < 15% relative standard deviation (RSD). Analyte stability during sampling processing and storage were established. Validation results on linearity, specificity, accuracy, precis...
Here we present a sensitive and specific liquid chromatography-tandem mass spectrometric method f... more Here we present a sensitive and specific liquid chromatography-tandem mass spectrometric method for the quantification of dimenhydrinate (I) in human plasma. Sample preparation is conducted using citalopram (II) addition as an internal standard (IS), liquid-liquid extraction with basified plasma using a mixture hexane/acetate (1:1, v/v) as the extracting solvent, and the final extract reconstituted in the mobile phase. I and II (IS) were injected in a C8 column with the mobile phase composed of methanol:isopropanol:water:formic acid (78.00:19.92:2.00:0.08, v/v/v/v) and monitored using a positive electrospray source with tandem mass spectrometry analyses. The selected reaction monitoring (SRM) was set using precursor ion and product ion combinations of m/z 256.0&gt;167.0 and m/z 325.0&gt;109.0 for I and II, respectively. The limit of quantification (LOQ) was 0.4 ng/mL, the dynamic range being 0.4-200 ng/mL. Validation results on linearity, specificity, accuracy, precision and stability, as well as on application to the analysis of plasma samples taken up to 24 h after oral administration of 100 mg of dimenhydrinate in healthy volunteers demonstrated its applicability to bioavailability studies.
The aim of the present study was to bring additional evidence regarding a biopredictive dissoluti... more The aim of the present study was to bring additional evidence regarding a biopredictive dissolution medium containing 1% sodium lauryl sulphate (SLS) to predict the in vivo behavior of carbamazepine (CBZ) products. Twelve healthy volunteers took one immediate release (IR) dose of either test and reference formulations in a bioequivalence study (BE). Dissolution profiles were carried-out using the medium. Level A in vitro–in vivo correlations (IVIVC) were established using both one-step and two-step approaches as well as exploring the time-scaling approach to account for the differences in dissolution rate in vitro versus in vivo. A detailed step by step calculation was provided to clearly illustrate all the procedures. The results show additional evidence that the medium containing 1% SLS can be classified as a universal biopredictive dissolution tool, and that both of the approaches used to develop the IVIVC (one and two-steps) provide good in vivo predictability. Therefore, this b...
A high incidence of positive cases for cannabinoids, in analyses for doping control in sports, ha... more A high incidence of positive cases for cannabinoids, in analyses for doping control in sports, has been observed since the International Olympic Committee (IOC) included them in the 1989 list of prohibited drugs under the title of classes of prohibited substances in certain circumstances. Where the rules of sports federations so provide, tests are conducted for marijuana, hashish or any other cannabis product exposure by means of urinalysis of 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (carboxy-THC) the main metabolite of delta-9-tetrahydrocannabinol (THC). Concentrations &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;15 ng/mL (cut-off value) in confirmatory analytical procedures are considered doping. Cannabis is an illicit drug in several countries and has received much attention in the media for its potential therapeutic uses and the efforts to legalise its use. Studies have demonstrated that the use of cannabinoids can reduce anxiety, but it does not have ergogenic potential in sports activities. An increase in heart rate and blood pressure, decline of cardiac output and reduced psychomotor activity are some of the pharmacological effects of THC that will determine a decrease in athletic performance. An ergolytic activity of cannabis products has been observed in athletes of several different sport categories. In Brazil, analyses for doping control in sports, performed in our laboratories, have detected positive cases for carboxy-THC in urine samples of soccer, volleyball, cycling and other athletes. It is our intention to discuss in this article some points that may discourage individuals from using cannabis products during sports activities, even in the so-called permitted circumstances defined by the IOC and some sports federations.
The study was developed to compare the in vitro dissolution profiles of pantoprazole (CAS 102625-... more The study was developed to compare the in vitro dissolution profiles of pantoprazole (CAS 102625-70-7) formulations in both The United States Pharmacopeia (USP) apparatus 2 and 3 by applying biorelevant medium. Moreover, an in vitro-in vivo relationship was proposed considering in vivo data from a previously published study. In vitro dissolution profiles were evaluated in biorelevant medium in USP apparatus 2 and 3 and the dissolution curves were either compared by the similarity factor (f2) or a model-independent approach. The fraction of drug dissolved in vitro in apparatus 2 was compared with the fraction of drug absorbed in vivo, which was obtained from a retrospective in vivo study. An in vitro-in vivo relationship analysis was then applied to elucidate the overall absorption characteristics of formulations. The dissolution profiles of formulations demonstrated similar disposition in biorelevant medium in both USP apparatus 2 and 3. The dissolution profiles were described by f2 model in apparatus 2 and Weibull&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s function in apparatus 3. The vitro-in vivo relationship analysis showed that the formulations exhibited permeability rate-limiting absorption. Biorelevant medium in both USP apparatus 2 and 3 may be used as a tool to predict in vivo disposition of formulations of pantoprazole. Furthermore, it can be argued that biowaiver can be granted for enteric coated formulations of pantoprazole on the basis of in vitro dissolution profile.
Revista Brasileira de Ciências Farmacêuticas, 2005
ABSTRACT Esteróides androgênicos anabólicos (EAA) são substâncias naturais, sintéticas ou semi-si... more ABSTRACT Esteróides androgênicos anabólicos (EAA) são substâncias naturais, sintéticas ou semi-sintéticas derivadas da testosterona, utilizadas em atividades esportivas com o objetivo de melhorar o desempenho físico pelo aumento de massa e força muscular. Apesar de causarem efeitos tóxicos graves, principalmente sobre os sistemas cardiovascular, hepático e neuro-endócrino, os EAA têm sido amplamente utilizados no âmbito esportivo. Desta forma, o presente trabalho teve como objetivo a validação de um método para a determinação de esteróides e/ou seus produtos de biotransformação em amostras de urina por cromatografia gasosa acoplada à espectrometria de massas (CG-EM). O método baseou-se na hidrólise enzimática de esteróides conjugados, no emprego da extração líquido-líquido e na derivação do extrato para posterior análise por CG-EM, no modo de monitoramento seletivo de íons (SIM). O método validado cumpriu com os princípios de confiança necessários para a determinação de EAA em amostras de urina com a finalidade de controle de dopagem no esporte. Os limites de detecção dos esteróides analizados variaram de 0,5 a 15 ng/mL. Bons valores de precisão (intra e interensaio) também foram obtidos (CV&lt; 11%). Amostras de voluntários (n=10) que relataram uso de EAA foram submetidas ao método. Pela análise das amostras, foi verificado o uso dos principais esteróides utilizados no âmbito esportivo no Brasil.
Uploads
Papers by Daniel Rossi de Campos