QbD-oriented development and validation of a bioanalytical method for nevirapine with enhanced liquid-liquid extraction and chromatographic separation

2015 ◽  
Vol 30 (6) ◽  
pp. 818-828 ◽  
Author(s):  
Sarwar Beg ◽  
Vandna Chaudhary ◽  
Gajanand Sharma ◽  
Babita Garg ◽  
Sagar Suman Panda ◽  
...  
Keyword(s):  
Chromatographic Separation ◽  
Liquid Extraction ◽  
Bioanalytical Method ◽  
Liquid Liquid Extraction ◽  
Development And Validation

scholarly journals The Development and Validation of a Novel Designer Benzodiazepines Panel by LC–MS-MS

2021 ◽  
Author(s):  
Rebecca A Mastrovito ◽  
Donna M Papsun ◽  
Barry K Logan
Keyword(s):  
Illicit Drug ◽  
Liquid Extraction ◽  
Electrospray Tandem Mass Spectrometry ◽  
Method Performance ◽  
Internal Standards ◽  
Liquid Liquid Extraction ◽  
Relative Standard ◽  
Development And Validation ◽  
Positive Ion ◽  
Designer Benzodiazepines

Abstract Novel illicit benzodiazepines are among the most active areas of new illicit drug manufacture and use. We describe a method for the detection and quantification of etizolam and its metabolite α-hydroxyetizolam, flubromazolam, clonazolam, diclazepam, delorazepam, bromazepam, flubromazepam, phenazepam, flualprazolam, flunitrazolam, and nitrazolam in human whole blood. After addition of internal standards, samples are buffered and extracted using a liquid–liquid extraction. Analysis is performed using positive-ion electrospray tandem mass spectrometry for detection and quantitation. Calibration ranges were established based on the method performance and differed from compound to compound. Replicates at the lowest calibration point for each compound performed within 5% of CV (Coefficient of Variation). The correlation coefficient was >0.990 for all compounds. Relative standard deviation for all compounds was ≤10% of CV and accuracy was  ±10% for both within- and between-run experiments. The maximum average intra- and inter-run imprecision were 5.7%. The maximum average intra- and inter-run imprecision was −8.7%. As part of evaluating the scope for relevancy, samples testing positive in immunoassay but confirmed to be negative in traditional benzodiazepine confirmation method were re-analyzed using this method. The presence of at least one novel benzodiazepine was identified in 70% of these samples. The appearance of these novel “designer” benzodiazepines demonstrates the challenge for toxicology testing and the need for continually updated confirmation methods.

Development and Validation of a Method for Quantification of 28 Psychotropic Drugs in Postmortem Blood Samples by Modified Micro-QuEChERS and LC–MS-MS

2020 ◽  
Author(s):  
Taís B Rodrigues ◽  
Damila R Morais ◽  
Victor A P Gianvecchio ◽  
Elvis M Aquino ◽  
Ricardo L Cunha ◽  
...  
Keyword(s):  
Sample Preparation ◽  
Forensic Toxicology ◽  
Sample Volume ◽  
Weighting Factor ◽  
Liquid Extraction ◽  
Analytical Toxicology ◽  
Limit Of Quantification ◽  
Liquid Liquid Extraction ◽  
Postmortem Blood ◽  
Development And Validation

Abstract The development of new sample preparation alternatives in analytical toxicology leading to quick, effective, automated and environmentally friendly procedures is growing in importance. One of these alternatives is the QuEChERS, originally developed for the analysis of pesticide residues, producing cleaner extracts than liquid–liquid extraction, and easier separation of aqueous and organic phases. However, there are few published studies on the miniaturization of this technique for forensic toxicology, especially in postmortem analysis. We developed and validated a modified micro-QuEChERS and LC–MS-MS assay to quantify 16 antidepressants, 7 antipsychotics and 3 metabolites and semi-quantify norfluoxetine and norsertraline in postmortem blood. The calibration curve was linear from 1 to 500 ng/mL, achieved an r > 0.99, with all standards quantifying within ±15% of target except ±20% at the limit of quantification of 1 ng/mL for 26 substances. The F test was applied to evaluate if the variance between replicates remained constant for all calibrators. Six weighting factors were analyzed (1/x, 1/x2, 1/x0,5, 1/y, 1/y2 and 1/y0,5), with the weighting factor with the lowest sum of residual regression errors (1/x2) selected. No endogenous or exogenous interferences were observed. Method imprecision and bias were <19.0% and 19.7%, respectively. Advantages of this method include a low sample volume of 100 µL, simple but effective sample preparation and a rapid 8.5-min run time. The validated analytical method was successfully applied to the analysis of 100 authentic postmortem samples.

Qualified method for the estimation of di-18:1 bis(monoacylglycero)phosphate in urine, a noninvasive biomarker to monitor drug-induced phospholipidosis

Bioanalysis ◽  
2020 ◽  
Vol 12 (15) ◽  
pp. 1049-1059
Author(s):  
Bokka Venkata Murali ◽  
Vishwanath Kurawattimath ◽  
Priyadeep Bhutani ◽  
Joelle Onorato ◽  
Sangmesh B Naikodi ◽  
...  
Keyword(s):  
Preclinical Study ◽  
Liquid Extraction ◽  
Urinary Biomarker ◽  
Drug Induced ◽  
Bioanalytical Method ◽  
Linearity Range ◽  
Liquid Liquid Extraction ◽  
Fivefold Increase ◽  
Noninvasive Biomarker ◽  
Study Methodology

Aim: Our objective was to develop and qualify a bioanalytical method for the estimation of di-18:1-bis(monoacylglycero)phosphate (di-18:1 BMP) as a urinary biomarker for the assessment of drug-induced phospholipidosis and demonstrate its application in a preclinical study. Methodology/results: di-18:1 BMP was extracted by liquid–liquid extraction using n-butanol and analyzed by LC–MS/MS. The qualified method was selective, precise, robust and accurate across the linearity range (0.2–250 ng/ml). Qualified method was then used to assess chloroquine-induced phospholipidosis in rats dosed at 120 mg/kg for 5 days. A fivefold increase in di-18:1 BMP was observed on Day 5 compared with predose. Conclusion: Di-18:1 BMP can be used as a noninvasive biomarker to assess/screen compounds that could cause drug-induced phospholipidosis in rats.

“BIOANALYTICAL METHOD DEVELOPMENT AND VALIDATION FOR ESTIMATION OF PROPOFOL IN K3EDTA HUMAN PLASMA BY USING LC-ESI-MS/MS”

2019 ◽  
Vol 8 (5) ◽  
Author(s):  
Ashok Kumar ◽  
Dr. D.B. Joshi ◽  
Dr. R.S. Bhadauria
Keyword(s):  
Quality Control ◽  
Analytical Method ◽  
Method Development ◽  
Solid Phase ◽  
Extraction Methods ◽  
Bioanalytical Method ◽  
Biological Matrix ◽  
Liquid Liquid Extraction ◽  
Method Development And Validation ◽  
Development And Validation

Bioanalytical method development is the process of creating a procedure to enable a compound of interest to be identified and quantified in a biological matrix. A compound can often be measured by several methods and the choice of analytical method involves many considerations. Analysis of drugs and their metabolites in a biological matrix is carried out using different extraction techniques like liquid-liquid extraction, solid phase extraction (SPE) and protein precipitation from these extraction methods samples are spiked with calibration (reference) standards and using quality control (QC) samples. These methods and choice of analytical method describes the process of method development and includes sampling, sample preparation, separation, detection and evaluation of the results. The developed process is then validated. These Bioanalytical validations play a significant role in evaluation and interpretation of bioavailability, bioequivalence, pharmacokinetic, and toxicokinetic studies. In which different parameters like accuracy, precision, selectivity, sensitivity, reproducibility, and stability are performed. Keywords: - LLE, SPE, Quality control samples, Bioequivalence, Bioavailability, Validation.

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