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

Autor: Murali BV; Pharmaceutical Candidate Optimization, Biocon Bristol Myers Squibb R&D Center (BBRC), Syngene International Limited, Biocon Park, Plot 2 & 3, Bommasandra IV Phase, Bangalore 560099, India., Kurawattimath V; Pharmaceutical Candidate Optimization, Biocon Bristol Myers Squibb R&D Center (BBRC), Syngene International Limited, Biocon Park, Plot 2 & 3, Bommasandra IV Phase, Bangalore 560099, India., Bhutani P; Pharmaceutical Candidate Optimization, Biocon Bristol Myers Squibb R&D Center (BBRC), Syngene International Limited, Biocon Park, Plot 2 & 3, Bommasandra IV Phase, Bangalore 560099, India., Onorato J; Bristol Myers Squibb, Princeton, NJ 08648, USA., Naikodi SB; Pharmaceutical Candidate Optimization, Biocon Bristol Myers Squibb R&D Center (BBRC), Syngene International Limited, Biocon Park, Plot 2 & 3, Bommasandra IV Phase, Bangalore 560099, India., Kole P; Pharmaceutical Candidate Optimization, Biocon Bristol Myers Squibb R&D Center (BBRC), Syngene International Limited, Biocon Park, Plot 2 & 3, Bommasandra IV Phase, Bangalore 560099, India., Rajanna PK; Pharmaceutical Candidate Optimization, Biocon Bristol Myers Squibb R&D Center (BBRC), Syngene International Limited, Biocon Park, Plot 2 & 3, Bommasandra IV Phase, Bangalore 560099, India.
Jazyk: angličtina
Zdroj: Bioanalysis [Bioanalysis] 2020 Aug; Vol. 12 (15), pp. 1049-1059. Date of Electronic Publication: 2020 Jul 31.
DOI: 10.4155/bio-2020-0114
Abstrakt: 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.
Databáze: MEDLINE
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