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The effects of special patient population plasma on pharmacokinetic quantifications using LC-MS/MS.

Abstract

BACKGROUND

Clinical development of lesinurad, a selective uric acid reabsorption inhibitor, required analysis of lesinurad in plasma from special patient populations. EMA and FDA bioanalytical method validation guidance have recommended studying matrix effects on quantitation if samples from special patient populations are to be analyzed. In addition to lesinurad (plasma protein binding 98.2%), the matrix effects from special population plasma on the quantitation of verapamil (PPB 89.6%), allopurinol and oxypurinol (PPB negligible) were also investigated.

RESULTS

The plasma from special population patients had no matrix effects on the three quantification methods with stable isotope labeled internal standard, protein precipitation extraction, and LC-MS/MS detection. The validated lesinurad plasma quantification method was successfully applied for the pharmacokinetic evaluations to support the clinical studies in renal impaired patients.

CONCLUSIONS

Special population plasma did not affect quantitation of drugs with a wide range of plasma protein binding levels in human plasma. With the confirmation that there is no impact on quantification from the matrix, the bioanalytical method can be used to support the pharmacokinetic evaluations for clinical studies in special populations.

Authors+Show Affiliations

Bioanalytical, Ardea Biosciences / AstraZeneca, San Diego. United States.. United States.Bioanalytical, Ardea Biosciences / AstraZeneca, San Diego. United States.Bioanalytical, Ardea Biosciences / AstraZeneca, San Diego. United States.Bioanalytical, Ardea Biosciences / AstraZeneca, San Diego. United States.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31613735

Citation

Zhou, Dongmei, et al. "The Effects of Special Patient Population Plasma On Pharmacokinetic Quantifications Using LC-MS/MS." Drug Metabolism Letters, 2019.
Zhou D, Sun L, Nguyen M, et al. The effects of special patient population plasma on pharmacokinetic quantifications using LC-MS/MS. Drug Metab Lett. 2019.
Zhou, D., Sun, L., Nguyen, M., Yeh, L. T., & Wilson, D. M. (2019). The effects of special patient population plasma on pharmacokinetic quantifications using LC-MS/MS. Drug Metabolism Letters, doi:10.2174/1872312813666191015162634.
Zhou D, et al. The Effects of Special Patient Population Plasma On Pharmacokinetic Quantifications Using LC-MS/MS. Drug Metab Lett. 2019 Oct 15; PubMed PMID: 31613735.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effects of special patient population plasma on pharmacokinetic quantifications using LC-MS/MS. AU - Zhou,Dongmei, AU - Sun,Lifang, AU - Nguyen,Mai, AU - Yeh,Li- Tain, AU - Wilson,David M, Y1 - 2019/10/15/ PY - 2018/04/25/received PY - 2019/09/18/revised PY - 2019/09/25/accepted PY - 2019/10/16/entrez PY - 2019/10/16/pubmed PY - 2019/10/16/medline KW - Hepatic impairment KW - LC-MS/MS KW - isobaric ions KW - plasma protein binding KW - protein precipitation KW - renal impairment JF - Drug metabolism letters JO - Drug Metab Lett N2 - BACKGROUND: Clinical development of lesinurad, a selective uric acid reabsorption inhibitor, required analysis of lesinurad in plasma from special patient populations. EMA and FDA bioanalytical method validation guidance have recommended studying matrix effects on quantitation if samples from special patient populations are to be analyzed. In addition to lesinurad (plasma protein binding 98.2%), the matrix effects from special population plasma on the quantitation of verapamil (PPB 89.6%), allopurinol and oxypurinol (PPB negligible) were also investigated. RESULTS: The plasma from special population patients had no matrix effects on the three quantification methods with stable isotope labeled internal standard, protein precipitation extraction, and LC-MS/MS detection. The validated lesinurad plasma quantification method was successfully applied for the pharmacokinetic evaluations to support the clinical studies in renal impaired patients. CONCLUSIONS: Special population plasma did not affect quantitation of drugs with a wide range of plasma protein binding levels in human plasma. With the confirmation that there is no impact on quantification from the matrix, the bioanalytical method can be used to support the pharmacokinetic evaluations for clinical studies in special populations. SN - 1874-0758 UR - https://www.unboundmedicine.com/medline/citation/31613735/The_effects_of_special_patient_population_plasma_on_pharmacokinetic_quantifications_using_LC-MS/MS DB - PRIME DP - Unbound Medicine ER -
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