Meloxicam determination in human plasma by high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS) in Brazilian bioequivalence studies.
OBJECTIVE
In this study, the bioavailability of 2 meloxicam 15 mg tablet formulations was compared. A single dose of each formulation was administered to 24 healthy volunteers (12 males and 12 females).


METHODS
The study was conducted using an open, randomized and crossover design with a 2-week washout interval. The plasma samples were obtained over a 96-hour interval and meloxicam concentrations were analyzed by high-performance liquid chromatography (an agilent) coupled to an API 2000 turboionspray tandem mass spectrometry (LC-MS-MS). An electrospray ionization (ESI) source operating in the positive ion mode, using a cross flow counter electrode and set for the multiple reaction monitoring (MRM) was employed. The plasma protein precipitate was reconstituted with acetonitrile/water + 10 mM acetic acid (20/80, v/v) and injected in a Prevail C8 5 microm (150 mm x 4.6 mm i.d.) analytical column with reverse-phase liquid chromatography. The retention time observed for meloxicam and tenoxicam (internal standard) was 1.8 and 1.4 minutes, respectively. The mean recovery of meloxicam was 95.9% and the limit ofquantification was 0.02 microg/ml.


RESULTS
The geometric mean of meloxicam/movatec 15 mg individual % ratio was 101.3% for AUC(last), 99.9% for AUC(0-infinity) and 107.7% for C(max). The 90% confidence intervals were 97.3 - 105.4%, 96.0 - 104.0% and 98.8 - 117.4%, respectively.


CONCLUSIONS
Since the 90% CI for both AUC(Iast), AUC(0-infinity) and C(max), ratios were all inside the 80 - 125% interval proposed by the US Food and Drug Administration Agency and accepted by Brazilian ANVISA (Sanitary Surveillance Agency), it was concluded that the meloxicam formulation produced by Merck S.A. lndústrias Químicas is bioequivalent to the movatec formulation regarding both the rate and extent of absorption. This assay method was faster, more simple, specific, precise and accurate in determining the bioequivalence of meloxicam than any method previously described.
Rigato
H Modesto
HM
Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil.
Mendes
G Duarte
GD
Borges
N Carter do Carmo
NC
Moreno
R A
RA
D000328:Adult; D019540:Area Under Curve; D001938:Brazil; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D000077239:Meloxicam; D012016:Reference Values; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013810:Therapeutic Equivalency; D013843:Thiazines / Q000097:blood / Q000493:pharmacokinetics*; D013844:Thiazoles / Q000097:blood / Q000493:pharmacokinetics*
D016861:Cyclooxygenase Inhibitors; D013843:Thiazines; D013844:Thiazoles; D000077239:Meloxicam