Determination of nabumetone and 6-methoxy-2-naphthylacetic acid in plasma using HPLC with UV and MS detection
Authors:
Lenka Nespěšná 1,2; Martin Štícha 1; Olga Matoušková 2; František Perlík 2; Ondřej Slanař 2
Authors place of work:
Univerzita Karlova v Praze, Katedra organické a jaderné chemie, Přírodovědecká fakulta
1; Univerzita Karlova v Praze, Farmakologický ústav 1. lékařské fakulty
2
Published in the journal:
Čes. slov. Farm., 2011; 60, 17-24
Category:
Original Articles
Summary
The study aimed to establish and validate an analytical method for the determination of nabumetone and 6-methoxy-2-naphthylacetic acid (6-MNA) in human plasma after a single therapeutic dose of the drug. Two methods based on HPLC with UV and MS detection were compared. Optimal results in sample preparation were achieved using solid phase extraction. The recovery reached approximately 84% and 86–90% for nabumetone and 6-MNA, respectively. A reverse C18 column was used for HPLC separation of the analytes. The limit of UV detection was 50 nM and 0.1 μM for 6-MNA and nabumetone, respectively. The limit of MS detection was 1 μM and 0.5 μM for 6‑MNA and nabumetone, respectively. Precision ranged between 4.2–14.4% and 4.6–8.5% using UV and MS detection for nabumetone, respectively. The respective values for 6-MNA were 2.4–12.5% and 2.1–9.4%. Accuracy ranged between 93.4–109.6% in UV detection and 86.2–107.9% using UV and MS detection for nabumetone, respectively. The respective values for 6-MNA were 87.8–107.4% and 86.3–106.4%. The method was subsequently applied to determine the pharmacokinetic parameters of nabumetone and 6-MNA in a group of 24 healthy volunteers.
Key words:
nabumetone – pharmacokinetics – 6-methoxy-2-naphthylacetic acid – HPLC – LC/MS
Zdroje
1. Boyle, E. A., Freeman, P. C., Mangan, F. R., Thomson, M. J.: Nabumetone (BRL 14777, 4-[6-methoxy-2-naphthyl]-butan-2-one): a new anti-inflammatory agent. J Pharm Pharmacol. 1982; 34, 562–569.
2. Battisti, W. P., Katz, N. P., Weaver, A. L., Matsumoto, A. K., Kivitz, A. J., Polis, A. B., Geba, G. P.: Pain management in osteoarthritis: a focus on onset of efficacy – a comparison of rofecoxib, celecoxib, acetaminophen, and nabumetone across four clinical trials. J Pain. 2004; 5, 511–520.
3. Hedner, T., Samulesson, O., Wahrborg, P., Wadenvik, H., Ung K. A., Ekbom, A.: Nabumetone: therapeutic use and safety profile in the management of osteoarthritis and rheumatoid arthritis. Drugs. 2004; 64, 2315–2343; discussion 2344–2315.
4. Kobylinska, K., Barlinska, M., Kobylinska, M.: Analysis of nabumetone in human plasma by HPLC. Application to single dose pharmacokinetic studies. J Pharm Biomed Anal. 2003; 32, 323–328.
5. Starek, M., Krzek, J.: A review of analytical techniques for determination of oxicams, nimesulide and nabumetone. Talanta. 2009; 77, 925–942.
6. Kendall, M. J., Chellingsworth, M. C., Jubb, R., Thawley, A. R., Undre, N. A., Kill, D. C.: A pharmacokinetic study of the active metabolite of nabumetone in young healthy subjects and older arthritis patients. Eur J Clin Pharmacol. 1989; 36, 299–305.
7. Davies, N. M.: Clinical pharmacokinetics of nabumetone. The dawn of selective cyclo-oxygenase-2 inhibition? Clin Pharmacokinet. 1997; 33, 404–416.
8. Patel, B. N., Sharma, N., Sanyal, M., Prasad, A., Shrivastav, P. S.: High-throughput LC-MS/MS assay for 6-methoxy-2-naphthylacetic acid, an active metabolite of nabumetone in human plasma and its application to bioequivalence study. Biomed Chromatogr. 2008; 22, 1213–1224.
9. Srinivas N. R.: Applicability of LC/MS/MS assay for 6-methoxy-2-napthylacetic acid to support the bioequivalence study of nabumetone-comments on the research work of Patel et al. (2008). Biomed Chromatogr. 2009; 23, 674–675.
10. Food and Drug Administration: FDA Guidance for Industry: Bioanalytical Method Validation. 2001; http://www.fda.gov/cder/quidance (15. 11. 2010).
Štítky
Pharmacy Clinical pharmacologyČlánok vyšiel v časopise
Czech and Slovak Pharmacy
2011 Číslo 1
Najčítanejšie v tomto čísle
- On teaching the chemistry of pharmaceutical auxiliary substances within the framework of pharmaceutical education in the Czech and Slovak Republics
- Study on 99mTc-MAG3 and 99mTc-DMSA renal accumulation using in vitro cellular model
- Determination of nabumetone and 6-methoxy-2-naphthylacetic acid in plasma using HPLC with UV and MS detection
- Determination of airborne and surface contamination with cyclophosphamide at the Masaryk Memorial Cancer Institute, Brno, Czech Republic