Nabumetone

Molecular formula: C15H16O2

Molecular weight: 228.3
CAS Registry No.: 42924-53-8

SAMPLE
Matrix: blood
Sample preparation: 2 mL Plasma + 200 |JLL 200 |xg/mL naproxen + 1 mL 500 mM pH
3 citrate buffer + 100 JJLL 1 M HCl + 5 mL ether, shake for 2 min, centrifuge. Remove
the organic layer and evaporate it to dryness, reconstitute the residue in MeCN, inject
an aliquot.
HPLCVARIABLES
Guard column: Resolve C18 Guard-Pak (Waters)
Column: C18 Radial-Pak (Waters)
Mobile phase: MeCN: sodium acetate buffer 60:40
Detector: UV 280
CHROMATOGRAM
Internal standard: naproxen
OTHER SUBSTANCES
Extracted: metabolites
KEYWORDS
plasma; pharmacokinetics
REFERENCE
Brier, M.E.; Sloan, R.S.; Aronoff, G.R. Population pharmacokinetics of the active metabolite of nabumetone in renal dysfunction. Clin.Pharmacol.Ther., 1995, 57, 622-627

SAMPLE
Matrix: blood
Sample preparation: 0.5 mL Plasma + 2.5 |xL 400 |xg/mL 6-chloro-2-naphthylacetic acid
in acetone, mix on a whirlmixer, add 6 mL n-hexane: ethyl acetate 50:50, add 0.7 mL 1.5
M HCl, shake mechanically for 30 min, centrifuge at 1500 g for 10 min. Remover organic
layer and evaporate it to dryness at 37 under a stream of nitrogen. Dissolve residue in
mobile phase, centrifuge, inject a 20 JJLL aliquot.
HPLCVARIABLES
Guard column: Lichrosorb RP-8
Column: 250 X 4.6 5 jxm Ultrasphere ODS
Mobile phase: MeOH: 50 mM pH 3.0 sodium acetate 70:30
Column temperature: 40
Flow rate: 1
Injection volume: 20
Detector: F ex 284 em 320 (cut-off)
CHROMATOGRAM
Retention time: 7
Internal standard: 6-chloro-2-naphthylacetic acid (6)
Limit of detection: 250 ng/mL

OTHER SUBSTANCES
Extracted: metabolites
Simultaneous: acetaminophen, aspirin, naproxen, salicylic acid
KEYWORDS
plasma
REFERENCE
Ray, J.E.; Day, R.O. High-performance liquid chromatographic determination of a new anti-inflammatory
agent, nabumetone, and its major metabolite in plasma using fluorimetric detection. J.Chromatogr.,
1984, 336, 234-238

SAMPLE
Matrix: blood, synovial fluid
Sample preparation: 100 [xL Plasma or synovial fluid + 200 fxL 2 mg/mL IS in MeCN,
vortex thoroughly, centrifuge at 11000 rpm for 5 min, inject an 80 \xL aliquot of the
supernatant. Tissue. Homogenize (Ultra-Turrax) 150 mg tissue with 600 (synovial membrane) or 1200 (fibrous capsule tissue) mg water for 1 min, vortex vigorously, sonicate for
30 min, vortex, centrifuge. Remove a 50 JULL aliquot and add it to 100 fxL 1 (synovial
membrane) or 0.33 (fibrous capsule tissue) mg/mL IS in MeCN, vortex thoroughly, centrifuge at 11000 rpm for 5 min, inject an 4 JJLL aliquot of the supernatant.
HPLCVARIABLES
Column: 150 X 3.9 Resolve 5 C18 (Waters)
Mobile phase: MeCN: 50 mM NaH2PO4 40:60, pH 5.2 (For the active metabolite, 6-methoxy-2-naphthylacetic acid, use MeCN: 50 mM NaH2PO4 30:70, pH 5.2.)
Flow rate: 1.6
Injection volume: 4-80
Detector: F ex 224 em 356
CHROMATOGRAM
Internal standard: BRL 24333
Limit of detection: <21 ng/mL
KEYWORDS
plasma; synovial membrane; fibrous capsule tissue
REFERENCE
Miehlke, R.K.; Schneider, S.; Sorgel, R; Muth, P.; Henschke, R; Giersch, K.H.; Miinzel, P. Penetration
of the active metabolite of nabumetone into synovial fluid and adherent tissue of patients undergoing
knee joint surgery. Drugs, 1990, 40 Suppl 5, 57-61