FDA Guidelines (fda + guideline)

Distribution by Scientific Domains


Selected Abstracts


A pharmacodynamic assessment of the impact of antihypertensive non-adherence on blood pressure control

PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 7 2000
DrPh, Peter W. Choo MD
Abstract Objectives To evaluate if antihypertensive regimens that conform to present FDA guidelines by maintaining ,,50% of their peak effect at the end of the dosing interval protect patients during sporadic lapses in adherence. Methods 169 patients on monotherapy for high blood pressure underwent electronic adherence monitoring for 3 months. Blood pressures were measured during non-study office visits and were retrieved from automated medical records. Questionnaires were used to obtain other covariate information. The ratio of the dosing interval to the half-life of drug activity (I,) was used to capture conformity with FDA guidelines. Data analysis focused on the interaction between I, and the impact on blood pressure of delayed dosing. Results The average (,,standard deviation) blood pressure during the study was 139.0 (,,12.0)/85.0 (,,6.9) mm Hg. Lisinopril followed by sustained-release verapamil, atenolol, and hydrochlorothiazide were the most frequently prescribed agents. The majority of regimens (99%) conformed to FDA dosing guidelines. Of the patients 23% missed a dose before their blood pressure check. Non-adherence, however, did not have a direct impact on blood pressure, and no interaction with I, of was detected. Conclusions Among patients with relatively mild hypertension on single-drug therapy, regimens that conform to current FDA dosing guidelines may prevent losses of blood pressure control during episodic lapses of adherence. These findings should be replicated in other patient populations with standardized blood pressure measurement to confirm their validity. Copyright 2000 John Wiley & Sons, Ltd. [source]


Biochemical and analytical development of the CIME cocktail for drug fate assessment in humans

RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 16 2010
Orianne Videau
Phenotyping based on drug metabolism activity appears to be informative regarding mechanism-based interactions during drug development. We report here the first steps of the development of the innovative CIME cocktail. This cocktail is designed not only for the major cytochrome P450, with caffeine, amodiaquine, tolbutamide, omeprazole, dextromethorphan and midazolam as substrates of CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A, respectively, but also phase II enzymes UGT 1A1/6/9 with acetaminophen, P-gp and OATP1B1 with digoxin and rosuvastatin, and renal function with memantine. An assay combining ultra-performance liquid chromatography using a 1.7,m particle size column with tandem mass spectrometry (UPLC/MS/MS) was set up for the simultaneous quantification of the 20 substrates and metabolites after extraction from human plasma using solid-phase extraction. The method was validated in the spirit of the FDA guidelines. Mean accuracy ranged from 87.7 to 115%, the coefficient of variance (CV%) of intra- and inter-run from 1.7 to 16.4% and from 1.6 to 14.9%, respectively, and for the limit of quantification (LOQ) with ten lots of plasma, accuracy ranged from 84 to 115% and CV% precision was <16%. Short-term stability was evaluated in eluate (4,h, room temperature), plasma (24,h, room temperature), the autosampler (24,h, 4C) and in three freeze/thaw cycles in plasma. All except three analytes were stable under these conditions. For the three others a specific process can be followed. This robust, fast and sensitive assay in human plasma provides an analytical tool for ten-probe drugs of the CIME cocktail. Clinical samples will be assayed in the near future using this new assay method. Copyright 2010 John Wiley & Sons, Ltd. [source]


Sensitive and selective liquid chromatography,tandem mass spectrometry method for the determination of metoclopramide in human plasma: application to a bioequivalence study

BIOMEDICAL CHROMATOGRAPHY, Issue 9 2010
Jaswanth Kumar Inamadugu
Abstract A simple, sensitive and rapid method has been developed and validated for determination of the metoclopramide (MCP) in 100,,L human plasma. The analytical procedure involves a liquid,liquid extraction method using tramadol as an internal standard (IS). Chromatographic separation was carried out on a HyPURITY ADVANCE column using a mobile phase consisting of acetonitrile and 10,mm ammonium acetate buffer in the ratio of 80:20 (v/v) at a flow rate of 0.3,mL/min. The total run time of analysis was 2.5,min and elution of MCP and IS occurred at 0.9 and 1.3,min, respectively. A linear response function was established for the range of concentrations 0.53,42.07,ng/mL (r > 0.99). The intra- and inter-day precision values for MCP met the acceptance as per FDA guidelines. MCP was stable in a battery of stability studies viz., bench-top, auto-sampler and freeze,thaw cycles. The developed assay method was successfully applied to an oral bioequivalence study in humans. Copyright 2010 John Wiley & Sons, Ltd. [source]


Quantification of montelukast, a selective cysteinyl leukotriene receptor (CysLT1) antagonist in human plasma by liquid chromatography,mass spectrometry: validation and its application to a human pharmacokinetic study

BIOMEDICAL CHROMATOGRAPHY, Issue 8 2009
D. Vijaya Bharathi
Abstract A highly sensitive, rapid assay method has been developed and validated for the estimation of montelukast (MTK) in human plasma with liquid chromatography coupled to tandem mass spectrometry with electro spray ionization in the positive-ion mode. Liquid,liquid extraction was used to extract MTK and amlodipine (internal standard, IS) from human plasma. Chromatographic separation was achieved with 10 mm ammonium acetate (pH 6.4): acetonitrile (15:85, v/v) at a flow rate of 0.50 mL/min on a Discovery HS C18 column with a total run time of 3.5 min. The MS/MS ion transitions monitored were 586.10 , 422.10 for MTK and 409.20 , 238.30 for IS. Method validation and clinical sample analysis were performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 0.25 ng/mL and linearity was observed from 0.25 to 800 ng/mL. The intra-day and inter-day precisions were 5.97,8.33 and 7.09,10.13%, respectively. This novel method has been applied to a pharmacokinetic study of MTK in humans. Copyright 2009 John Wiley & Sons, Ltd. [source]


Development and validation of a highly sensitive and robust LC-ESI-MS/MS method for simultaneous quantitation of simvastatin acid, amlodipine and valsartan in human plasma: application to a clinical pharmacokinetic study,

BIOMEDICAL CHROMATOGRAPHY, Issue 6 2009
Addepalli V. Ramani
Abstract A high-throughput, simple, highly sensitive and specific LC-MS/MS method has been developed for simultaneous estimation of simvastatin acid (SA), amlodipine (AD) and valsartan (VS) with 500 L of human plasma using deuterated simvastatin acid as an internal standard (IS). The API-4000 LC-MS/MS was operated under the multiple reaction-monitoring mode (MRM) using electrospray ionization. The assay procedure involved precipitation of SA, AD, VS and IS from plasma with acetonitrile. The total run time was 2.8 min and the elution of SA, AD, VS and IS occurred at 1.81, 1.12, 1.14 and 1.81 min, respectively; this was achieved with a mobile phase consisting of 0.02 m ammonium formate (pH 4.5):acetonitrile (20:80, v/v) at a flow rate of 0.50 mL/min on an X-Terra C18 column. A linear response function was established for the range of concentrations 0.5,50 ng/mL (r > 0.994) for VS and 0.2,50 ng/mL (r > 0.996) for SA and AD. The method validation parameters for all three analytes met the acceptance as per FDA guidelines. This novel method has been applied to human pharmacokinetic study. Copyright 2009 John Wiley & Sons, Ltd. [source]


Highly sensitive method for the determination of ropinirole with a lower limit of quantitation of 3.45 pg/mL in human plasma by LC-ESI-MS/MS: application to a clinical pharmacokinetic study

BIOMEDICAL CHROMATOGRAPHY, Issue 5 2009
D. Vijaya Bharathi
Abstract A highly sensitive, rapid assay method has been developed and validated for the estimation of ropinirole (RPR) in human plasma with liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive-ion mode. A solid-phase process was used to extract RPR and citalopram (internal standard, IS) from human plasma. Chromatographic separation was operated with 0.2% ammonia solution:acetonitrile (20:80, v/v) at a flow rate of 0.50 mL/min on a Hypurity C18 column with a total run time of 3.2 min. The MS/MS ion transitions monitored were 261.2 , 114.2 for RPR and 325.1 , 209.0 for IS. Method validation and clinical sample analysis were performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 3.45 pg/mL and the linearity was observed from 3.45 to 1200 pg/mL. The intra-day and inter-day precisions were in the range of 4.71,7.98 and 6.56,8.31%, respectively. This novel method has been applied to a pharmacokinetic study of RPR in humans. Copyright 2008 John Wiley & Sons, Ltd. [source]


Highly sensitive method for the determination of omeprazole in human plasma by liquid chromatography,electrospray ionization tandem mass spectrometry: application to a clinical pharmacokinetic study

BIOMEDICAL CHROMATOGRAPHY, Issue 4 2009
Shivva Vittal
Abstract A highly sensitive, rapid assay method has been developed and validated for the estimation of omeprazole (OPZ) in human plasma with liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive-ion mode. The assay procedure involves alkalinization of plasma followed by simple liquid,liquid extraction of OPZ and lansoprazole (internal standard, IS) from human plasma with acetonitrile. Chromatographic separation was achieved with 0.01 m ammonium acetate:acetonitrile (40:60, v/v) at a flow rate of 0.25 mL/min on an Inertsil ODS 3 column with a total run time 2.5 min. The MS/MS ion transitions monitored were 346.1 , 198.1 for OPZ and 370.1 , 252.1 for IS. Method validation and clinical sample analysis were performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 0.05 ng/mL and the linearity was observed from 0.05 to 10.0 ng/mL. The intra-day and inter-day precisions were in the ranges 2.09,8.56 and 5.29,8.19%, respectively. This novel method has been applied to a pharmacokinetic study of OPZ in humans. Copyright 2008 John Wiley & Sons, Ltd. [source]


Development and validation of a sensitive LC-MS/MS method with electrospray ionization for quantitation of pramipexole in human plasma: application to a clinical pharmacokinetic study

BIOMEDICAL CHROMATOGRAPHY, Issue 2 2009
D. Vijaya Bharathi
Abstract A highly sensitive and specific LC-MS/MS method has been developed and validated for the estimation of pramipexole (PPX) with 500 L human plasma using memantine as an internal standard (IS). The API-4000 was operated under multiple-reaction monitoring mode (MRM) using the electrospray ionization technique. Solid-phase extraction was used to extract PPX and IS from human plasma. The resolution of peaks was achieved with 0.01 m ammonium acetate buffer (pH 4.4):acetonitrile (30:70, v/v) on a Discovery CN column. The total chromatographic run time was 3.0 min and the elution of PPX and IS occurred at approximately 2.32 and 2.52, respectively. The MS/MS ion transitions monitored were 212.10 , 153.10 for PPX and 180.20 , 107.30 for IS. The method was proved to be accurate and precise at linearity range of 20,3540 pg/mL with a correlation coefficient (r) of ,0.999. The intra- and inter-day precision and accuracy values found to be within the assay variability limits as per the FDA guidelines. The developed assay method was applied to a pharmacokinetic study in human volunteers following oral administration of 0.25 mg PPX tablet. Copyright 2008 John Wiley & Sons, Ltd. [source]


Development and validation of a sensitive LC-MS/MS method with electrospray ionization for quantitation of zafirlukast, a selective leukotriene antagonist in human plasma: application to a clinical pharmacokinetic study

BIOMEDICAL CHROMATOGRAPHY, Issue 6 2008
D. Vijaya Bharathi
Abstract A highly sensitive and specific LC-MS/MS method has been developed and validated for the estimation of zafirlukast (ZFK) with 500 L human plasma using valdecoxib as an internal standard (IS). The API-4000 LC-MS/MS was operated under multiple reaction-monitoring mode using the electrospray ionization technique. The assay procedure involved extraction of ZFK and IS from human plasma with ethyl acetate. The resolution of peaks was achieved with 10 mm ammonium acetate (pH 6.4):acetonitrile (20:80, v/v) on a Hypersil BDS C18 column. The total chromatographic run time was 2.0 min and the elution of ZFK and IS occurred at approximately 1.11 and 1.58 min, respectively. The MS/MS ion transitions monitored were 574.2 , 462.1 for ZFK and 313.3 , 118.1 for IS. The method was proved to be accurate and precise at a linearity range of 0.15,600 ng/mL with a correlation coefficient (r) of ,0.999. The method was rugged with 0.15 ng/mL as lower limit of quantitation. The intra- and inter-day precision and accuracy values were found to be within the assay variability limits as per the FDA guidelines. The developed assay method was applied to a pharmacokinetic study in human volunteers following oral administration of 20 mg ZFK tablet. Copyright 2008 John Wiley & Sons, Ltd. [source]


Development and validation of a sensitive LC-MS/MS method with electrospray ionization for quantitation of doxofylline in human serum: application to a clinical pharmacokinetic study

BIOMEDICAL CHROMATOGRAPHY, Issue 6 2008
Nimmagadda Sreenivas
Abstract A highly sensitive and specific LC-MS/MS method has been developed and validated for the estimation of doxofylline (DFL) with 300 L human serum using imipramine as the internal standard (IS). The API-3000 LC-MS/MS was operated under multiple reaction-monitoring mode using the electrospray ionization technique. The assay procedure involved direct precipitation of DFL and IS from human serum with acetonitrile. The resolution of peaks was achieved with formic acid (pH 2.5):acetonitrile (10:90, v/v) on an Amazon C18 column. The total chromatographic run time was 3.0 min and the elution of DFL and IS occurred at approximately 1.46 and 2.15 min, respectively. The MS/MS ion transitions monitored were 267.5 , 181.1 for DFL and 281.1 , 86.2 for IS. The method was proved to be accurate and precise at linearity range of 1.00,5000 ng/mL with a correlation coefficient (r) of ,0.999. The method was rugged with 1.00 ng/mL as lower limit of quantitation. The intra- and inter-day precision and accuracy values were found to be within the assay variability limits as per the FDA guidelines. The developed assay method was applied to a pharmacokinetic study in human volunteers following oral administration of DFL tablet. Copyright 2008 John Wiley & Sons, Ltd. [source]


Quantitative analysis of docetaxel in human plasma using liquid chromatography coupled with tandem mass spectrometry

BIOMEDICAL CHROMATOGRAPHY, Issue 5 2005
I. E. L. M. Kuppens
Abstract An assay for the quantitative determination of docetaxel in human plasma is described. Docetaxel was extracted from the matrix using liquid,liquid extraction with ter -butylmethylether, followed by high-performance liquid chromatographic analysis using an alkaline eluent. Paclitaxel was used as internal standard. Positive ionization electrospray tandem mass spectrometry was performed for selective and sensitive detection. The method was validated according to the FDA guidelines on bioanalytical method validation. The validated range for docetaxel was from 0.25,1000 ng/mL using 200 L plasma aliquots. The method requires only a limited volume (200 L) of human plasma and the method can be applied in studies requiring a low lower limit of quantitation of 0.25 ng/mL. The assay was applied successfully in several clinical and pharmacological studies with docetaxel. Copyright 2004 John Wiley & Sons, Ltd. [source]


Parent-proxy report of their children's health-related quality of life: an analysis of 13 878 parents' reliability and validity across age subgroups using the PedsQL 4.0 Generic Core Scales

CHILD: CARE, HEALTH AND DEVELOPMENT, Issue 5 2007
Richard Reading
Parent-proxy report of their children's health-related quality of life: an analysis of 13 878 parents' reliability and validity across age subgroups using the PedsQL 4.0 Generic Core Scales . VarniJ. W., LimbersC. A. & BurwinkleT. M. ( 2007 ) Health and Quality of Life Outcomes , 5 , 2 . DOI:10.1186/1477-7525-5-2. Background, Health-related quality of life (HRQOL) measurement has emerged as an important health outcome in clinical trials, clinical practice improvement strategies, and healthcare services research and evaluation. While paediatric patient self-report should be considered the standard for measuring perceived HRQOL, there are circumstances when children are too young, too cognitively impaired, too ill or fatigued to complete an HRQOL instrument, and reliable and valid parent-proxy report instruments are needed in such cases. Further, it is typically parents' perceptions of their children's HRQOL that influences healthcare utilization. Data from the PedsQL DatabaseSM were utilized to test the reliability and validity of parent-proxy report at the individual age subgroup level for ages 2,16 years as recommended by recent Food and Drug Administration (FDA) guidelines. Methods, The sample analysed represents parent-proxy report age data on 13 878 children ages 2,16 years from the PedsQL 4.0 Generic Core Scales DatabaseSM. Parents were recruited from general paediatric clinics, sub-specialty clinics and hospitals in which their children were being seen for well-child checks, mild acute illness or chronic illness care (n = 3,718, 26.8%), and from a State Children's Health Insurance Program in California (n = 10 160, 73.2%). Results, The percentage of missing item responses for the parent-proxy report sample as a whole was 2.1%, supporting feasibility. The majority of the parent-proxy report scales across the age subgroups exceeded the minimum internal consistency reliability standard of 0.70 required for group comparisons, while the total scale scores across the age subgroups approached or exceeded the reliability criterion of 0.90 recommended for analysing individual patient scale scores. Construct validity was demonstrated utilizing the known groups approach. For each PedsQL scale and summary score, across age subgroups, healthy children demonstrated a statistically significant difference in HRQOL (better HRQOL) than children with a known chronic health condition, with most effect sizes in the medium-to-large effect size range. Conclusion, The results demonstrate the feasibility, reliability and validity of parent-proxy report at the individual age subgroup for ages 2,16 years. These analyses are consistent with recent FDA guidelines which require instrument development and validation testing for children and adolescents within fairly narrow age groupings and which determine the lower age limit at which reliable and valid responses across age categories are achievable. Even as paediatric patient self-report is advocated, there remains a fundamental role for parent-proxy report in paediatric clinical trials and health services research. [source]


Determination of bevantolol enantiomers in human plasma by coupled achiral,chiral high performance-liquid chromatography

CHIRALITY, Issue 7 2007
Joung Weon Oh
Abstract A coupled achiral,chiral high performance liquid chromatographic method was developed and fully validated for the determination of bevantolol enantiomers, (,)-(S)-bevantolol and (+)-(R)-bevantolol, in human plasma. Plasma samples were prepared by solid phase extraction with Sep-Pak Plus C18 cartridges followed by HPLC. Bevantolol enantiomers and (+)-(R)-Propranolol as internal standard (IS) were preseparated from interfering components in plasma on a Phenomenex silica column and bevantolol enantiomers and IS were resolved and determined on a Chiralcel OJ-H chiral stationary phase. The two columns were connected by a switching valve equipped with silica precolumn. The Precolumn was used to concentrate bevantolol in the eluent from the achiral column before back flushing onto chiral phase. A detailed validation of the method was performed accordingly to FDA guidelines. For each enantiomer the assay was linear between 20 and 1600 ng/ml. The quantification limits of both bevantolol enantiomers were 20 ng/ml. The intraday variation was between 1.07 and 12.64% in relation to the measured concentration and the interday variation was 0.91 and 11.79%. The method has been applied to the determination of (,)-(S)- and (+)-(R)-bevantolol in plasma from healthy volunteers dosed with racemic bevantolol hydrochloride. hydrochloride. Chirality, 2007. 2007 Wiley-Liss, Inc. [source]