A Novel Analytical Method for the Estimation of Solriamfetol in Plasma Samples by Lc-Ms/Ms

2021 ◽  
Vol 11 (5) ◽  
Author(s):  
Ratnakumari Perina. ◽  
Kannappan N. ◽  
Premkumar P.
Keyword(s):  
Correlation Coefficient ◽  
Internal Standard ◽  
The United States ◽  
Single Step ◽  
Array Detector ◽  
Plasma Samples ◽  
Validation Parameters ◽  
Norepinephrine Reuptake Inhibitor ◽  
United States Food ◽  
Us Fda

Solriamfetol is a selective dopamine and norepinephrine reuptake inhibitor with wake‐promoting effects. The aim of the present study is to develop a rapid, sensitive and reliable method for the estimation of Solriamfetol in plasma samples using LC-MS. In the present investigation, a rapid, specific, selective and novel method has been optimized for evaluation of solriamfetol in in plasma using modafinil as an internal standard and identification of degradants by LC-MS/MS. The solriamfetol and internal standard were extracted from plasma in a single step using acetonitrile. The principle analytes were eluted with the conditions of mobile phase having the 5mM ammonium format in methanol: 50% Methanol in acetonitrile (90:10%, v/v). The Chromatographic column used is Xterra MS C18, 3.5µ.m, 1mmX150mm analytical column with the 0.5 ml/min flow rate. The detector is CEM array detector. The retention times of solriamfetol and modafinil were 1.50min-1.51min with a total run time of 3 min. The curve indicates correlation coefficient (r2) for modafinil was superior by having the value 1.000 with linear range of 5ng/ml to 500ng/ml. The correlation coefficient (r2) for solriamfetol was found to be 0.999. The LOQ and LOD for the solriamfetol was 33.70pg/ml and 11.12pg/ml respectively The developed method was validated by evaluating system suitability, selectivity, sensitivity, linearity, precision, accuracy, ruggedness and stability in conformity with the guidelines of the United States Food and Drug Administration (US-FDA). The results of validation parameters were found to be within the acceptance limits. Hence, the developed and validated method can be utilized for the routine determination of solriamfetol in plasma samples.

scholarly journals An audit of US FDA warning letters issued to sponsors, institutional review boards and investigators over a six-year period

2021 ◽  
pp. 01-06
Author(s):  
Unnati Saxena ◽  
Debdipta Bose ◽  
Shruti Saha ◽  
Nithya J Gogtay ◽  
Urmila M Thatte
Keyword(s):  
Adverse Drug Events ◽  
The United States ◽  
Institutional Review Boards ◽  
Chi Square ◽  
Institutional Review ◽  
United States Food ◽  
Post Marketing ◽  
Chi Square Test ◽  
Us Fda ◽  
Review Boards

The present audit was carried out with the objective of evaluating warning letters (WLs) issued to trial sponsors, clinical investigators and institutional review boards (IRBs) by the United States Food and Drug Administration during a six-year period and compare it with two similar earlier audits. WLs were reviewed and classified as per stakeholders and further categorised as per predefined violation themes. The chi-square test was performed for trend analysis of WLs. A total of 62 WLs were issued to the three stakeholders. The maximum number of WLs were issued to the clinical investigators (36/62, 58.06%), followed by sponsors (19/62, 30.64%), and least to the IRBs (7/62, 11.29%). Among sponsors, lack of standard operating procedures for the monitoring, receipt, evaluation and reporting of post-marketing adverse drug events was the most common violation theme (8/19, 42.1%). Among clinical investigators, deviation from investigational plan was the most common violation theme (31/36, 86.11%.). For IRBs, inadequate documentation was the most common violation theme (6/7, 85.71%). We saw an overall reduction in the number of WLs issued to the stakeholders. Thus, we identified multiple areas on which each stakeholder should work for improvement.

US FDA Warning Letters of CAPA Violations: A Review

2020 ◽  
Vol 7 (2) ◽  
pp. 85-92
Author(s):  
Pavan Deshpande ◽  
Rutuja Agawane ◽  
Sarath C. Tatikola ◽  
Surenahalli G. Vasantharaju
Keyword(s):  
United States ◽  
Drug Administration ◽  
The United States ◽  
Quality And Safety ◽  
Drug Substances ◽  
Warning Letter ◽  
End Products ◽  
United States Food ◽  
States Food ◽  
Us Fda

United States Food and Drug Administration (USFDA) is a federal agency functioning under United States Federal Executive Departments, which strives to regulate the food products and drug substances being manufactured or brought into US market, upholding Quality and Safety as prime goals. It takes care of its goals by inspecting firms which market products in the United States. It chalks out good manufacturing procedures for obtaining quality end-products. Based on inspections conducted and data collected thereby, those not abiding by rules shall be issued with Warning Letters and marketing license shall be cancelled for those who fail to justify the warning letter. This brings about discipline amongst manufacturers and sets a goal of quality that needs to be achieved to survive in market.

scholarly journals DEVELOPMENT AND VALIDATION OF RP-HPLC METHOD FOR THE DETERMINATION OF ALVIMOPAN IN RAT PLASMA

2018 ◽  
Vol 10 (10) ◽  
pp. 124
Author(s):  
Devi Ramesh ◽  
Mohammad Habibuddin
Keyword(s):  
Method Development ◽  
Internal Standard ◽  
The United States ◽  
Hplc Method ◽  
Liquid Extraction ◽  
Pharmacokinetic Parameters ◽  
Dihydrogen Phosphate ◽  
Liquid Liquid Extraction ◽  
Validation Parameters

Objective: The present investigation demonstrates a simple, sensitive and accurate high pressure liquid chromatographic (HPLC) method for the determination of alvimopan (AMP) in rat plasma.Methods: The chromatographic separation was achieved within 10 min by using acetonitrile: potassium dihydrogen phosphate buffer pH 3.0 adjusted with orthophosphoric acid (50:50) as mobile phase on Altima Grace Smart C-18 column (5μ; 250 × 4.6 mm) at a flow rate of 1.0 ml/min with injection volume 50 µl. The drug was extracted from plasma by liquid-liquid extraction using a mixture of methanol: acetonitrile (50:50) as a solvent. The retention times of drug and internal standard were found to be 5.17 and 6.74 min, respectively. This method was validated as per the United States Food and Drug Administration (US-FDA) guidelines.Results: The results of the validation parameters were found to be within the acceptance limits. The method was linear in the concentration range from 5-1000 ng/ml (r2= 0.9998), and the extraction recovery was found to be 78.71±3.86% for AMP. The lower limit of quantification was found to be 5ng/ml, and the stability of recovered samples at different conditions was found to be more than 95%.Conclusion: The developed method possess good selectivity, specificity, there was no interference found in the plasma blanks at retention times of AMP and Internal Standard (IS). We found a good correlation between the peak area and concentration of the drug under prescribed conditions. Furthermore, the method can also be used to estimate the pharmacokinetic parameters of AMP.Keywords: Alvimopan, Liquid-liquid extraction, Method development, Matrix effect, Plasma, Recovery, Stability, Validation

scholarly journals The United States Food and Drug Administration's Approach to Training International Suppliers in Food Safety and Security

2006 ◽  
Vol 16 (4) ◽  
pp. 566-569 ◽  
Author(s):  
James W. Rushing ◽  
Christopher S. Walsh
Keyword(s):  
Food Safety ◽  
Safety Information ◽  
Agricultural Practices ◽  
The United States ◽  
Train The Trainer ◽  
United States Food ◽  
Us Fda ◽  
Training Examples ◽  
Programming Plans ◽  
The U.S

In 1998 the U.S. Food and Drug Administration (US-FDA) published formal guidelines for the microbial safety of fresh produce. The guidelines identify and suggest the use of good agricultural practices (GAP) and good manufacturing practices (GMP) for producers and handlers. To extend this important information to international producers and suppliers, an agreement was made to create a GAP and GMP training program through the Joint Institute for Food Safety and Applied Nutrition (JIFSAN). JIFSAN combined resources of US-FDA, the University of Maryland, and other universities to reach audiences outside the U.S. with food safety information. The program is based on the train-the-trainer concept. Its success depends on the ability of the newly trained program participants to reach key audiences in the target country. We present an overview of the development of a training manual and its content, the selection of a teaching team and target countries, and the methods for implementation of the training. Examples of activities in various countries are summarized. Results of a program review conducted in 2004, following nine program deliveries, are also discussed. Future needs are identified and current programming plans are provided.

An audit of Black Box Warnings (BBWs) in the United States Food and Drug Administration (US-FDA) database - a five-year analysis

2021 ◽  
Vol 16 ◽  
Author(s):  
Debdipta Bose ◽  
Nithya Gogtay ◽  
Tejusv Goel ◽  
Mahanjit Konwar
Keyword(s):  
The United States ◽  
Black Box ◽  
Primary Objective ◽  
Molecular Entity ◽  
Therapeutic Class ◽  
The Us ◽  
United States Food ◽  
Black Box Warnings ◽  
States Food ◽  
Us Fda

Background: The black-box warning (BBW) is the most serious warning that US-FDA can ask for on a drug’s labelling. BBWs represent key safety concerns uncovered either during dossier review or post-approval. We have conducted the present study with the primary objective of assessing BBWs issued by the US-FDA. Methods: BBW’s were identified on US-FDA’s website from 1st January 2015 to 31st December 2019. Prescribing information was used to identify and characterize BBWs into new and minor/major update on a previous BBW. The therapeutic class of the drug, nature [Biological/New Molecular entity (NME)], formulation type, expected duration of use along with the year of first approval of the molecule with BBWs were evaluated. Results: A total of n = 167 BBWs were issued by FDA of which 53 (31.7%) had major updates, 57(34.1%) had minor updates and 57(34.1%) were new BBWs. A total of 137(82%) of BBWs were with NME’s whereas 30(18%) were with biologics. Drugs for neurology 40(25.5%)had the highest number of BBWs followed by oncology 38(24.2%). Among type of BBWs, cardiovascular risk 31 (15%) were the highest. Conclusion: Practicing physicians need to understand that benefit-risk of a drug is dynamic and keep abreast of new data related to it.

Efficacy and Cardiovascular Safety of DPP-4 Inhibitors

2020 ◽  
Vol 15 ◽  
Author(s):  
Nikhila A Subrahmanyan ◽  
Rithika Mary Koshy ◽  
Koshy Jacob ◽  
Joseph M Pappachan
Keyword(s):  
Polycystic Ovary ◽  
Meta Analysis ◽  
Safety Data ◽  
The United States ◽  
Cardiovascular Safety ◽  
Nonalcoholic Fatty Liver ◽  
Incretin Mimetics ◽  
Dipeptidyl Peptidase 4 ◽  
United States Food ◽  
Us Fda

: Dipeptidyl peptidase-4 (DPP-4) inhibitors or gliptins belong to the class of incretin mimetics, one important group of antidiabetic medications. These drugs were available in the market for management of type 2 diabetes mellitus (T2DM) over a decade. Sitagliptin, linagliptin, vildagliptin, saxagliptin and alogliptin are the common drugs from gliptin family widely available globally, whilst anagliptin, gemigliptin and teneliptin are used mainly in the Asian countries. The glycemic control conferred by gliptins varies among individual molecules with an average reduction of glycated hemoglobin (HbA1c) ranging between –0.5 to –1.0% with monotherapy. Additive effects on HbA1c reduction may result from combination therapy with other antidiabetics. Weak evidence from various studies suggests that gliptins may be useful in treating nonalcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS). Gliptin's safety in not established in pregnancy, and there is only meager evidence of use in T2DM among children. In line with the United States Food and Drug Administration (US FDA) recommendations, sitagliptin, linagliptin, saxagliptin and alogliptin have undergone rigorous cardiovascular outcomes outcome trials (CVOTs) in recent years, and the safety data for vildagliptin is available through retrospective analysis of various studies in meta-analysis. Small clinical trial- and meta-analysis- based data are available for the CV safety of other DPP-4 inhibitors also. In general, the CVOTs and other safety data do not reveal serious warning signals except for saxagliptin (higher risk of hospitalization from heart failure [hHF]), although there is no robust data on the risk of hHF among patients with moderate to severe HF at baseline treated with other gliptins. This review critically appraises the efficacy and cardiovascular safety of DPP-4 inhibitors to empower clinicians to use this class of antidiabetic medications judiciously.

scholarly journals Development and Validation of UPLC-MS/MS Method for the Determination of Aripiprazole in Rat Plasma Using Liquid-Liquid Extraction: Pharmacokinetic and Bioequivalence Application

2020 ◽  
Vol 32 (10) ◽  
pp. 2671-2676
Author(s):  
Ashish Raghuvanshi ◽  
Urooj A. Khan ◽  
Uzma Parveen ◽  
Anshul Gupta ◽  
Gaurav K. Jain
Keyword(s):  
Internal Standard ◽  
Rat Plasma ◽  
Liquid Extraction ◽  
Single Step ◽  
Liquid Liquid Extraction ◽  
Validation Parameters ◽  
Tandem Mass Spectrometric ◽  
Liquid Chromatographic

A selective, simple, sensitive and rapid ultra-performance liquid chromatographic tandem mass spectrometric (UPLC-MS/MS) method for the detection of aripiprazole in rat plasma has been developed and validated using aripiprazole-D8 as internal standard (IS). A simple single step sample preparation process was accomplished by liquid-liquid extraction (LLE). The post-treatment samples were chromato-graphed and analyzed on a UPLC bridged ethyl hybrid (BEH) C-18 column using mobile phase composition of acetonitrile: 0.1% formic acid in water::70:30 (v/v). Aripiprazole was analyzed by MS detector in positive electrospray ionization mode (ESI). Multiple reactions monitoring (MRM) was employed to observed the transition for aripiprazole (m/z 448.35→285.09) and aripiprazole-D8 (m/z 456.2→293.2). The developed method was validated and found linear in the working range of 2-1025 ng/mL with correlation coefficient, r2 = 0.99951 and quantification limit of 2.02 ng/mL. All validation parameters were in accordance with the ICH guidelines and met the acceptance criteria. The method was found to be accurate (recovery, 97.07 to 103.64%, precise (% CV, 2.68 to 7.70%), rapid (run time 4 min) and specific. The validated method was successfully used for the determination of plasma concentration of aripiprazole after single oral administration in rats and hence could be useful for in vivo pharmacokinetic study and bioequivalence testing of aripiprazole formulations.

scholarly journals Management Options in Advanced Prostate Cancer: What is the Role for Sipuleucel-T?

2011 ◽  
Vol 5 ◽  
pp. CMO.S5977 ◽  
Author(s):  
Rhonda L. Bitting ◽  
Andrew J. Armstrong ◽  
Daniel J. George
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial Data ◽  
The United States ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Management Options ◽  
Castration Resistant ◽  
United States Food ◽  
States Food ◽  
Us Fda

Most prostate cancer-related deaths occur in patients with castration-resistant prostate cancer (CRPC). Until recently, only therapy with docetaxel and prednisone has been shown to prolong survival in men with metastatic CRPC. With the United States Food and Drug Administration (US FDA) approvals of sipuleucel-T, cabazitaxel, and abiraterone acetate, all based on improvement in overall survival, the landscape for management of men with metastatic CRPC has dramatically changed. In this review we will discuss the pivotal clinical trial data leading to these approvals, with particular focus on the unique indication for sipuleucel-T and the implications for optimal management and sequencing of treatment in this patient population.

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