RESUMEN
A specific, fast and sensitive high performance liquid chromatography coupled to an electro spray tandem triple quadrupole mass spectrometer (LC-MS/MS) assay was developed for the determination of nimesulide in human plasma using carbamazepine as the internal standard. The lower limit of quantification (LLOQ) was 50 ng/ml and the calibration curves were linear in the concentration range of 50 - 6,000 ng/ml. Method inter-batch precision and accuracy ranged from 2.78 to 10.80%, and 94.92 to 102.46%, respectively. Intra-batch precision ranged from 2.44 to 7.74%, while intra-batch accuracy ranged from 91.70 to 104.73%. The analytical method was applied to evaluate the pharmacokinetic and relative bioavailability of two different pharmaceutical formulations containing nimesulide, one tablet and one oral suspension, manufactured by the same pharmaceutical factory, comparing with two reference Nisulid formulations in 52 volunteers of both sexes previously divided in two groups of 26 subjects (13 men and 13 females each group). The test tablet formulation was not bioequivalent to the Nisulid 100 mg tablet with respect to the rate of absorption, but was bioequivalent according to the extent of drug absorption. On the other hand, since the 90% CI for Cmax, AUC0-t and AUCinf were within the 80 - 125% interval in the oral suspension study, it was concluded that test oral suspension were bioequivalent to Nisulid 50 mg/ml with respect to both the rate and extent of absorption.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacocinética , Cromatografía Líquida de Alta Presión/métodos , Sulfonamidas/farmacocinética , Espectrometría de Masas en Tándem/métodos , Administración Oral , Adolescente , Adulto , Antiinflamatorios no Esteroideos/administración & dosificación , Área Bajo la Curva , Disponibilidad Biológica , Brasil , Estudios Cruzados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Espectrometría de Masa por Ionización de Electrospray/métodos , Sulfonamidas/administración & dosificación , Suspensiones , Comprimidos , Equivalencia Terapéutica , Adulto JovenRESUMEN
A rapid, sensitive and specific method to quantify diclofenac in human plasma using indomethacin as the internal standard (IS) is described. Samples were extracted using protein precipitation protocol and analyzed by high performance liquid chromatography coupled to ultraviolet detection at 276 nm. Chromatography was performed isocratically with a run time of 8.0 min and the retention time observed for diclofenac and IS was 6.0 and 7.0 min, respectively. The calibration curve was linear over the range 50 - 4,000 ng/ml (r2 > 0.9995). The mean recovery of diclofenac ranged from 88.76 to 99.14% and the limit of quantification was 50 ng/ml. Intrabatch precision and accuracy (%CV) of the method ranged from 0.86 to 7.60%, and 99.34 to 103.8%, respectively. Interbatch precision (%CV) and accuracy ranged from 0.26 to 11.4%, and 92.00 to 105.34%, respectively. This HPLC method was used to determine the relative pharmacokinetics of two diclofenac-cholestyramine 140 mg capsule formulations. The study was conducted using an open, randomized and crossover design with a 1-week washout interval. A single 140 mg dose (equivalent to 70 mg of diclofenac) of each formulation was administered to 26 healthy volunteers (13 males and 13 females) and blood samples were obtained over 12-h interval. The geometric mean of diclofenac-cholestyramine/Flotac ratio was 90.53% for AUC0-12 and 100.22% for Cmax. Since the 90% CI for Cmax and AUCs ratios were all inside the 80 - 125% interval, it was concluded that the diclofenac-cholestyramine test formulation is bioequivalent to Flotac regarding both the rate and the extent of absorption.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacocinética , Cromatografía Líquida de Alta Presión/métodos , Diclofenaco/farmacocinética , Adulto , Antiinflamatorios no Esteroideos/administración & dosificación , Área Bajo la Curva , Disponibilidad Biológica , Cápsulas , Resina de Colestiramina/administración & dosificación , Resina de Colestiramina/farmacocinética , Estudios Cruzados , Diclofenaco/administración & dosificación , Combinación de Medicamentos , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Equivalencia Terapéutica , Adulto JovenRESUMEN
OBJECTIVE: The aim of this study was to evaluate the performance of 2 phenoxymethylpenicillin 500,000 UI tablet formulations in healthy human volunteers. MATERIAL AND METHODS: The study was conducted using an open, randomized crossover design with a 7-day washout interval. A single dose of each formulation was administered to 26 healthy volunteers as assessed by clinical and laboratory test evaluations. The plasma samples were obtained over an 8-h interval and phenoxymethylpenicillin concentrations were quantified by a suitable and validated HPLC-UV method with detection at 220 nm. Systolic and diastolic blood pressure and pulse rate measurement were taken pre dose and at intervals up to 8 h. RESULTS: Tolerance of both products was adequate. The mean of Meracilina/Pen-Ve-Oral 500,000 UI% geometric mean was 99.89% for AUC0-t, 100.86% for AUC0-infinity and 101.11% for Cmax. The 90% confidence intervals were 94.62 - 105.46%, 95.22 - 106.83% and 98.61 - 103.87%, respectively. The mean recovery of phenoxymethylpenicillin was 94.8%, while the retention time observed for phenoxymethylpenicillin and phenytoin (internal standard) was 4 and 10 min, respectively. The limit of quantification was 0.10 mg/l. CONCLUSION: Since the 90% CI for AUC0-t, AUC0-infinity and Cmax ratios were all within the 80 - 125% interval proposed by the US FDA and accepted by ANVISA, it was concluded that the Meracilina formulation (manufactured by AchA(c) S.A.) is bioequivalent to Pen-Ve-Oral (manufactured by Eurofarma) for both the rate and the extent of bioavailability.
Asunto(s)
Antibacterianos/farmacocinética , Penicilina V/farmacocinética , Adulto , Antibacterianos/sangre , Área Bajo la Curva , Disponibilidad Biológica , Química Farmacéutica , Femenino , Voluntarios Sanos , Humanos , Masculino , Penicilina V/sangre , Comprimidos , Equivalencia TerapéuticaRESUMEN
OBJECTIVE: To assess the bioequivalence of a ramipril 5 mg tablet formulation (ramipril test formulation from Laboratórios Biosintética Ltda (Sao Paulo, Brazil) and Triatec from Aventis Pharma (Sueano, Brazil) standard reference formulation) in 26 healthy volunteers of both sexes. METHODS: The study was conducted using an open, randomized, 2-period crossover design with a 2-week washout interval. Plasma samples were obtained over a 36-hour period. Plasma ramipril and ramiprilat concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reaction monitoring (MRM). From the ramipril and ramiprilat plasma concentration vs. time curves, the following pharmacokinetic parameters were obtained: AUClast, AUCinf and Cmax. RESULTS: The limit of quantification was 0.2 ng x ml(-1) and 1.0 ng x ml(-1) for ramipril and ramiprilat, respectively. The geometric means and 90% confidence intervals (CI) for Ramipril/Triatec and Ramiprilat/Triatec percent ratios were: 104.69% (90% CI = 93.21-117.59%) for Cmax, 102.49% (90% CI = 92.76-113.24%) for AUClast, 103.60% (90% CI = 93.56 114.73%) for AUCinf, 108.48% (90% CI = 98.86-119.03%) for Cmax, 105.88% (90% CI = 101.55-110.39%) for AUClast, 97.30% (90% CI = 90.17-104.99%) for AUCinf, respectively. CONCLUSION: Since the 90% CI for AUClast, AUCinf and Cmax ratios were within the 80-125% interval proposed by the U.S. FDA, it was concluded that the ramipril formulation produced by Laboratórios Biosintética Ltda is bioequivalent to the Triatec formulation in both rate and extent of absorption.