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 ◽  
...  

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.

2019 ◽  
Vol 57 (7) ◽  
pp. 600-605 ◽  
Author(s):  
Venkata Krishna Reddy ◽  
Narayana Swamy ◽  
Rajeswari Rathod ◽  
Pinaki Sengupta

Abstract A simple and sensitive bioanalytical HPLC–UV method has been developed and validated for quantification of eliglustat in rat plasma. The liquid–liquid extraction method was found to be more efficient compared to protein precipitation technique. Chromatographic separation of eliglustat was achieved using Kromasil C18 column with a mobile phase consisting of a mixture of methanol and ammonium acetate (pH 3.2) in a ratio of 60:40. Detection wavelength was set at 282 nm. The developed method was specific, accurate, precise with good recovery and stability profile. The calibration curve constructed over a range of 0.3–10 μg/mL was linear (R2 > 0.997). Accuracy in intra and inter-day assay were found to be 96.27–107.35% and 96.80–106.57%, respectively. The corresponding precision (%CV) values were within 4.31–10.90% and 4.82–9.97%, respectively. Till date, no method is available for bioanalysis of eliglustat in any type of biological matrix. This is the first time to report a bioanalytical method for this molecule. The developed bioanalytical method was applied to quantitate eliglustat in the plasma samples of a single dose oral pharmacokinetic study in Sprague Dawley rat.


1983 ◽  
Vol 15 (6-7) ◽  
pp. 149-159 ◽  
Author(s):  
V C Blok ◽  
G P Slater ◽  
E M Giblin

Several commercially available adsorbents were compared with solvent extraction methods for their utility in recovering trace organics from water. The adsorbents examined included Amberlite XAD-2, XAD-4 and XAD-8, Ambersorb XE340 and XE348 and Tenax-GC. All were found to produce high artifact levels, even after extensive clean-up, making them unsuitable for the analysis of trace organics in water. Quantitatively, Likens-Nickerson or continuous liquid-liquid extraction with méthylene chloride gave better recoveries than the adsorbents. Qualitatively, extractive methods were preferred as they yielded much lower levels of impurities than the adsorbents. These methods of recovering trace organics were evaluated using a standard mixture of compounds added to the water at a level of 55 µg/l. Likens-Nickerson extraction gave comparable recoveries of this mixture at 55 µg/l and 11 µg/l.


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