Abstract
A sensitive and specific liquid chromatography–electrospray ionization–tandem mass spectrometry method has been developed and validated for the identification and quantification of brivudine in human plasma using diclofenac as an internal standard. The method involves extraction with ethyl acetate. The analyte was separated on a C18 column and analyzed in multiple reaction monitoring mode with a negative electrospray ionization interface using the [M–H]− ions, m/z 332.8→m/z 80.9 for brivudine, m/z 293.6→m/z 249.5 for diclofenac. The method was validated over the concentration range of 5.54–2,836 μg L−1 for brivudine. The intra-and inter-day precisions were less than 8.91% in terms of relative standard deviation (RSD), and the accuracy was within −4.22% in terms of relative error (RE). The lower limit of quantification (LLOQ) was 5.54 μg L−1 with acceptable precision and accuracy. There were almost no matrix effects. Recovery of brivudine spiked in drug-free plasma was higher than 77.17%. The method was used to study the pharmacokinetic profile of brivudine in human plasma after oral administration of brivudine tablets.
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10337-011-2001-y/MediaObjects/10337_2011_2001_Fig1_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10337-011-2001-y/MediaObjects/10337_2011_2001_Fig2_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10337-011-2001-y/MediaObjects/10337_2011_2001_Fig3_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10337-011-2001-y/MediaObjects/10337_2011_2001_Fig4_HTML.gif)
Similar content being viewed by others
References
Saijo M, Suzutani T, Mizuta K, Kurane I, Morikawa S (2008) Arch Virol 153:303–314. doi:10.1007/s00705-007-1096-9
Keam SJ, Chapman TM, Figgitt DP (2004) Drugs 64:2091–2097
Aksoy B, Altaykan-Hapa A, Cengiz A, Aksoy HM, Atakan N (2010) Eur J Dermatol 20:247–248. doi:10.1684/ejd.2010.0894
Rabasseda X (2003) Drugs of Today 39:359–371
De Clercq E (1986) Anticancer Res 6:549–556
Ayisi NK, Wall RA, De clercq E, Sacks SL (1986) J Chromatogr 375:423–430
Robinson Y, Gerry N, Vose CW (1985) J Chromatogr 338:219–224
Reeuwijk H, Tjaden UR, van der Greef J (1999) Journal of Chromatography B 726:269–276
Olgemoller J, Hempel G, Boos J, Blaschke G (1999) J Chromatogr B 726:261–268
Chen LY, Qin F, Ma YY, Li FM (2007) J Chromatogr B Anal Tech Biomed Life Sci 855:255–261. doi:10.1016/j.jchromb.2007.05.016
Brodie RR, Hill HM (2002) Chromatographia 55:S91–S94
Taylor PJ (2005) Clin Biochem 38:328–334. doi:10.1016/j.clinbiochem.2004.11.007
Karnes HT, March C (1993) Pharm Res 10:1420–1426
Shah VP, Midha KK, Findlay JW, Hill HM, Hulse JD, McGilveray IJ, McKay G, Miller KJ, Patnaik RN, Powell ML, Tonelli A, Viswanathan CT, Yacobi A (2000) Pharm Res 17:1551–1557
Tan ZR, Chen Y, Zhou G, Cao S, Peng XD, Wang YC, Peng XJ, Zhang W, Zhou HH (2010) Chromatographia 72:1107–1113. doi:10.1365/s10337-010-1797-1
Acknowledgments
This work was supported by the National Scientific Foundation of China (No.30801421, 30873089, 81001471, 30901834) and the Basic Science Research Fund in Central South University (2010QZZD010).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Peng, XD., Tan, ZR., Wu, HZ. et al. LC–MS–MS Quantitative Determination of Brivudine in Human Plasma and Its Application to Pharmacokinetic Studies. Chromatographia 73, 1089–1095 (2011). https://doi.org/10.1007/s10337-011-2001-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10337-011-2001-y