A rapid and simple determination of A77 1726 in human serum by high-performance liquid chromatography and its application for optimization of leflunomide therapy.

Journal of Pharmaceutical and Biomedical Analysis
E N van RoonJ R B J Brouwers

Abstract

Leflunomide is a disease-modifying antirheumatic drug, which is bioactivated by formation of A77 1726. In this study a rapid and simple quantitative assay using a reversed phase HPLC-UV method is validated for detection of A77 1726 in human serum. The HPLC-UV method uses a mobile phase consisting of methanol and a KH2PO4-buffer (45 mM, pH = 3) (50:50,v/v), at a flow rate of 1 mL/min. A77 1726 is detected by UV-absorption at 295 nm with a retention time of 8.9 min. Demoxepam is used as internal standard. Validation showed lower and upper limits of quantitation of 0.5 and 100 mg/L, respectively. The assay was linear over the concentration range of 0.5-100 mg/L (r2 > 0.999). Intra- and inter-day precision showed coefficients of variation within 15% over the complete concentration range; accuracy was within 8%. Commonly prescribed drugs to treat rheumatoid arthritis like disease-modifying antirheumatic drugs, analgesics and corticosteroids, and their main metabolites, are separated from A77 1726 with a resolution >2. Serum levels of A77 1726 in 37 patients on leflunomide therapy were determined using this HPLC-UV method. Measured serum A77 1726 serum concentrations in patient samples showed large variability with a range of 3-176 m...Continue Reading

References

Jun 21, 2002·Clinical Pharmacokinetics·Blaz Rozman
Aug 15, 2002·Annals of the Rheumatic Diseases·P GeborekUNKNOWN South Swedish Arthritis Treatment Group
Apr 6, 2004·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Vivien ChanSusan E Tett
May 21, 2004·British Journal of Clinical Pharmacology·E N Van RoonJ R B J Brouwers

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Citations

May 23, 2008·European Journal of Clinical Pharmacology·Petra Bohanec GrabarVita Dolzan
Aug 24, 2006·Apoptosis : an International Journal on Programmed Cell Death·D Y LegerJ L Beneytout
Jan 16, 2007·Annals of the Rheumatic Diseases·J M van WoerkomJ W J Bijlsma
Aug 21, 2015·Journal of Chromatographic Science·A Suneetha, Raja K Rajeswari
Feb 26, 2011·Journal of Pharmaceutical and Biomedical Analysis·Halima RakhilaMichael Wiese
Apr 4, 2016·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Panoraia I SiafakaDimitrios N Bikiaris
Oct 11, 2005·Environmental Management·T H Snelder, K F D Hughey
Jan 1, 2006·Expert Review of Clinical Immunology·Gary Kunkel, Grant W Cannon
Feb 14, 2020·Journal of Veterinary Internal Medicine·Todd M ArcherAndrew J Mackin
Dec 20, 2014·Therapeutic Drug Monitoring·Geoffrey S RuleKamisha L Johnson-Davis

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