scholarly journals Tandem Mass Spectrometry (MS/MS) in the Preclinical Pharmacokinetic Study of a Highly Prescribed SNRI Drug for Depression and Its Application to Oral Extended Release Solid Dosage Formulations in Rabbits

2021 ◽  
Author(s):  
Abdul Aala Fazli ◽  
Bala Krishna Panigrahy ◽  
Varinder Kumar ◽  
Syed Naiem Raza ◽  
Bilal Ahmad Zarger ◽  
...  
Keyword(s):  
Extended Release ◽  
Solid Phase ◽  
Preliminary Evidence ◽  
Ion Source ◽  
Formulation Development ◽  
Bioanalytical Method Validation ◽  
Bioanalytical Method ◽  
Solid Dosage ◽  
Depression Disorders ◽  
Us Fda

Abstract Preclinical pharmacokinetic (pK) studies in animal models during the formulation development phase give preliminary evidence and near clear picture of the pK behavior of drug and/or its dosage forms prior to clinical studies on humans and help in tailoring of the dosage form according to the expected and requisite clinical behavior. The present work reports first of its kind preclinical pK study on oral extended release (ER) solid dosage formulations of venlafaxine (VEN) in New Zealand White rabbits. The VEN is a highly prescribed and one of the safest and most effective therapeutic agents used in the treatment different types of depression disorders worldwide. The LC-MS/MS bioanalytical method developed for this purpose demonstrated enough reliability in simultaneously quantitating VEN and its equipotent metabolite O-desmethylvenlafaxine (ODV) in rabbit plasma. The method described uses solid phase extraction for sample preparation followed by an ultra-fast LC-MS/MS analysis. The chromatographic separation was achieved isocratically with a predominantly polar mobile phase by employing RPLC. The triple quadrupole LC/MS/MS system operated in MRM mode used an ESI probe as an ion source in positive polarity. The validation results are within the permissible limits of US FDA recommendations and acceptance criteria for bioanalytical method validation.

8th GCC: Consolidated feedback to US FDA on the 2013 Draft FDA Guidance on Bioanalytical Method Validation

Bioanalysis ◽  
2014 ◽  
Vol 6 (22) ◽  
pp. 2957-2963 ◽  
Author(s):  
Joseph Bower ◽  
Douglas Fast ◽  
Fabio Garofolo ◽  
Dominique Gouty ◽  
Roger Hayes ◽  
...  
Keyword(s):  
Method Validation ◽  
Bioanalytical Method Validation ◽  
Bioanalytical Method ◽  
Fda Guidance ◽  
Us Fda

Conference Report: AAPS and US FDA Crystal City V meeting on Quantitative Bioanalytical Method Validation and Implementation: feedback from the EBF

Bioanalysis ◽  
2014 ◽  
Vol 6 (6) ◽  
pp. 729-732 ◽  
Author(s):  
John Smeraglia ◽  
Stuart McDougall ◽  
Karen Elsby ◽  
Arjen Companjen ◽  
Stephen White ◽  
...  
Keyword(s):  
Method Validation ◽  
Conference Report ◽  
Bioanalytical Method Validation ◽  
Bioanalytical Method ◽  
Us Fda

scholarly journals Development and Validation of a Method for Quantification of Favipiravir as COVID-19 Management in Spiked Human Plasma

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3789
Author(s):  
Mohammad Hailat ◽  
Israa Al-Ani ◽  
Mohammed Hamad ◽  
Zainab Zakareia ◽  
Wael Abu Dayyih
Keyword(s):  
Human Plasma ◽  
Internal Standard ◽  
Weighting Factor ◽  
Hplc Method ◽  
Bioanalytical Method Validation ◽  
Spiked Human Plasma ◽  
Fda Guidance ◽  
Significant Difference ◽  
Us Fda ◽  
Carry Over

In the current work, a simple, economical, accurate, and precise HPLC method with UV detection was developed to quantify Favipiravir (FVIR) in spiked human plasma using acyclovir (ACVR) as an internal standard in the COVID-19 pandemic time. Both FVIR and ACVR were well separated and resolved on the C18 column using the mobile phase blend of methanol:acetonitrile:20 mM phosphate buffer (pH 3.1) in an isocratic mode flow rate of 1 mL/min with a proportion of 30:10:60 %, v/v/v. The detector wavelength was set at 242 nm. Maximum recovery of FVIR and ACVR from plasma was obtained with dichloromethane (DCM) as extracting solvent. The calibration curve was found to be linear in the range of 3.1–60.0 µg/mL with regression coefficient (r2) = 0.9976. However, with acceptable r2, the calibration data’s heteroscedasticity was observed, which was further reduced using weighted linear regression with weighting factor 1/x. Finally, the method was validated concerning sensitivity, accuracy (Inter and Intraday’s % RE and RSD were 0.28, 0.65 and 1.00, 0.12 respectively), precision, recovery (89.99%, 89.09%, and 90.81% for LQC, MQC, and HQC, respectively), stability (% RSD for 30-day were 3.04 and 1.71 for LQC and HQC, respectively at −20 °C), and carry-over US-FDA guidance for Bioanalytical Method Validation for researchers in the COVID-19 pandemic crisis. Furthermore, there was no significant difference for selectivity when evaluated at LLOQ concentration of 3 µg/mL of FVIR and relative to the blank.

scholarly journals Recommendations and Best Practices for Reference Standards and Reagents Used in Bioanalytical Method Validation

2014 ◽  
Vol 16 (2) ◽  
pp. 352-356 ◽  
Author(s):  
Joseph F. Bower ◽  
Jennifer B. McClung ◽  
Carl Watson ◽  
Takahiko Osumi ◽  
Kátia Pastre
Keyword(s):  
Best Practices ◽  
Method Validation ◽  
Reference Standards ◽  
Bioanalytical Method Validation ◽  
Bioanalytical Method

scholarly journals Sample Preparation and Extraction in Small Sample Volumes Suitable for Pediatric Clinical Studies: Challenges, Advances, and Experiences of a Bioanalytical HPLC-MS/MS Method Validation Using Enalapril and Enalaprilat

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Bjoern B. Burckhardt ◽  
Stephanie Laeer
Keyword(s):  
Sample Preparation ◽  
Solid Phase Extraction ◽  
Method Development ◽  
Matrix Effects ◽  
Solid Phase ◽  
Scale Up ◽  
Small Sample ◽  
Positive Pressure ◽  
Phase Extraction ◽  
Bioanalytical Method

In USA and Europe, medicines agencies force the development of child-appropriate medications and intend to increase the availability of information on the pediatric use. This asks for bioanalytical methods which are able to deal with small sample volumes as the trial-related blood lost is very restricted in children. Broadly used HPLC-MS/MS, being able to cope with small volumes, is susceptible to matrix effects. The latter restrains the precise drug quantification through, for example, causing signal suppression. Sophisticated sample preparation and purification utilizing solid-phase extraction was applied to reduce and control matrix effects. A scale-up from vacuum manifold to positive pressure manifold was conducted to meet the demands of high-throughput within a clinical setting. Faced challenges, advances, and experiences in solid-phase extraction are exemplarily presented on the basis of the bioanalytical method development and validation of low-volume samples (50 μL serum). Enalapril, enalaprilat, and benazepril served as sample drugs. The applied sample preparation and extraction successfully reduced the absolute and relative matrix effect to comply with international guidelines. Recoveries ranged from 77 to 104% for enalapril and from 93 to 118% for enalaprilat. The bioanalytical method comprising sample extraction by solid-phase extraction was fully validated according to FDA and EMA bioanalytical guidelines and was used in a Phase I study in 24 volunteers.

Sign in / Sign up

Export Citation Format

Share Document