Challenges in the indirect quantitation of acyl-glucuronide metabolites of a cardiovascular drug from complex biological mixtures in the absence of reference standards

Biomedical Chromatography

Volumn 24, Issue 7, 2010, Pages 759-767

  Srinivasan, Karthik ^a   Nouri, Parya ^b   Kavetskaia, Olga ^b  

^a Ferring Pharmaceuticals   (United States)

^b PFIZER INC   (United States)

Author keywords

Acyl glucuronide; Base hydrolysis; Indirect measurement; Mass spectrometry; Metabolites; Quantitation

Indexed keywords

ALKALINITY; ASSAYS; BIOMOLECULES; BODY FLUIDS; MASS SPECTROMETRY; METABOLITES; SODIUM HYDROXIDE;

ACYL-GLUCURONIDE; AGLYCONES; BASE HYDROLYSIS; GLUCURONIDE METABOLITES; GLUCURONIDES; INDIRECT MEASUREMENTS; LC-MS-MS; QUANTITATION; REFERENCE STANDARD; STUDY SAMPLES;

HYDROLYSIS;

ACYLGLUCURONIDE; DRUG METABOLITE; GLUCURONIDE; TORCETRAPIB; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; BIOTRANSFORMATION; HYDROLYSIS; IN VIVO STUDY; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; MONKEY; NONHUMAN; QUANTITATIVE ANALYSIS;

EID: 77953494804     PISSN: 02693879     EISSN: 10990801     Source Type: Journal    
DOI: 10.1002/bmc.1360     Document Type: Article

References (15)

1. Bailey MJ and Dickinson RG. Acyl glucuronide reactivity in perspective: biological consequences. Chemico-Biological Interactions 2003; 145: 117-137.
2. Baillie TA. Chemically reactive metabolites in drug discovery and development. In Drug Metabolizing Enzymes: Cytochrome p450 and Other Enzymes in Drug Discovery and Development. Marcel Dekker: New York, 2003; 147-154.
3. Dalvie D, Chen W, Zhang C, Vaz AD, Smolarek TA, Cox LM, Lin J and Obach RS. Pharmacokinetics, metabolism and excretion of torcetrapib in humans. Drug Metabolism and Disposition 2008; 36: 2185-2198.
4. Faed EM. Properties of acyl glucuronides: implications for studies of the pharmacokinetics and metabolism of acidic drug. Drug Metabolism Reviews 1984; 15: 1213-1249.
5. Fura A, Shu Y, Zhu M, Hanson RL, Ronngta V and Humphreys WG. Discovering drugs through biological transformation: role of pharmacologically active metabolites in drug discovery. Journal of Medicinal Chemistry 2004; 47: 4339-4351. (Pubitemid 39096823)
6. Hop CECA. LC-MS in drug disposition and metabolism. In The Encyclopedia of Mass Spectrometry. Elsevier: Amsterdam, 2006; 3: 233-274.
7. Kalgutkar AS, Gardner I, Obach RS, Shaffer CL, Callegari E, Henne KR, Mutlib AE, Dalvie DK, Lee JS, Nakai Y, O'Donnell JP, Boer J and Harriman SP. A comprehensive listing of bioactivation pathways of organic functional groups. Current Drug Metabolism 2005; 6: 161-225. (Pubitemid 40753853)
8. Obach RS. Drug-drug interactions: an important negative attribute in drugs. Drug Discovery Today 2003; 39: 301-338
9. Prakash C, Chen W, Rossulek M, Johnson K, Zhang C, O'Connell T, Potchoiba M and Dalvie D. Metabolism, pharmacokinetics and excretion of a cholesterol ester transfer protein inhibitor, torcetrapib, in rats, monkeys, and mice: characterization of unusual and novel metabolites by high-resoulution liquid chromatography-tandem mass spectrometry and 1H nuclear magnetic resonance. Drug Metabolism and Disposition 2008; 36: 2064-2079.
10. Prakash C, Shaffer CL and Nedderman A. Analytical strategies for identifying drug metabolites. Mass Spectrometry Reviews 2007; 26: 340-369.
11. Rodrigues AD. Drug-Drug Interactions. Drugs and the Pharmaceutical Sciences, Marcel Dekker: New York, 2002; 650.
12. Rozman KK and Klaassen CD. Absorption, distribution and excretion of toxicants. Casarett & Doull's Toxicology, The Basic Science of Poisons. McGraw-Hill: New York, 1995; 91-112.
13. Shipkova M, Armstrong VW, Oellerich M and Wieland E. Acyl glucuronide drug metabolites: toxicological and analytical implications. Therapeutic Drug Monitoring 2003; 15: 1-16.
14. Valaskovic GA, Utley L, Lee MS and Wu JT. Ultra-low flow nanospray for the normalization of conventional LC/MS through equimolar response: standard-free quantitative estimation of metabolite levels in drug discovery. Rapid Communications in Mass Spectrumetry 2006; 20(7): 1087-196.
15. Williams DA. Drug Metabolism. Foye's Principles of Medicinal Chemistry, 5th edn. Lippincott Williams & Wilkins: Philadephia, PA, 2002; 174-233.