The Elimination Profiles of Tenoxicam and Hydroxytenoxicam in Equine Urine and Serum after a 200-mg Oral Dose*

Abstract

Tenoxicam (Mobiflex) was administered orally to four standardbred mares at a dose of 200 mg. Elimination profiles of tenoxicam and hydroxytenoxicam were generated based on quantitation of these analytes in urine and serum by liquid chromatography (LC) with ultraviolet detection. Tenoxicam was confirmed by LC-tandem mass spectrometry daughter ion mass spectra in the last postadministration sample in which tenoxicam was detected. The tenoxicam and hydroxytenoxicam urinary elimination profiles had the same shape for the same horse; however, each horse was significantly different from the others. One horse (Horse 15) showed a much broader and flatter elimination profile than the other horses. Each horse had a peak in analyte concentration at different collection times. The latest detection for both tenoxicam and hydroxytenoxicam was 29-31 h for all horses. The urinary tenoxicam limit of detection (LOD) and limit of quantitation (LOQ) were 0.3 and 0.4 microg/mL, respectively. The urinary hydroxytenoxicam LOD and LOQ were 0.6 and 0.8 microg/mL, respectively. Hydroxytenoxicam was found to be completely conjugated and tenoxicam completely unconjugated in equine urine. Serum elimination profiles of tenoxicam were measured to 120 h postadministration. Hydroxytenoxicam was not detected in postadministration serum. The last serum tenoxicam detection was at the 24-h collection time for all horses. The peak average concentration was 434.5 ng/mL at 3 h. The serum tenoxicam LOD and LOQ were 5.7 and 7.3 ng/mL.

The detection of piroxicam, tenoxicam and their metabolites in equine urine by electrospray ionisation ion trap mass spectrometry

“…Phase II metabolism in the form of β ‐glucuronide conjugation was investigated by hydrolysis with E. coli β ‐glucuronidase enzyme and was found to be negligible. This is consistent with previous results obtained for meloxicam and its metabolites5, 6 and tenoxicam,3 but differs in the case of 5′‐hydroxytenoxicam from the observation of Marland et al ,3 where the equine tenoxicam metabolite was found to be β ‐glucuronide conjugated exclusively. The reason for this discrepancy is not immediately obvious.…”

“…Analogous fragmentation patterns have previously been reported for the closely related drug meloxicam and its metabolites acquired under the same conditions 5, 6. The positive ion atmospheric pressure chemical ionisation triple quadrupole product ion mass spectra of meloxicam,7 piroxicam7 and tenoxicam3 are also very similar, although prominent fragments in the former two cases deriving from cleavage of the thiazole ring ( m/z 73) and loss of the pyridine ring ( m/z 78), respectively, fall below the fragmentation cutoff of the ion trap and are not seen here. Under negative ion conditions all compounds were deprotonated with ion trap CID resulting only in a loss of sulfur dioxide as reported previously for meloxicam and its metabolites 4…”

“…Both compounds are known to be metabolised in humans primarily by hydroxylation of the pyridinyl substituent at the 5′‐position (Fig. 1),1, 2 and in the case of tenoxicam this transformation has also been confirmed in the horse 3. No study of the equine metabolism of piroxicam has yet been published.…”

“…In addition, confirmatory analyses of small molecules must currently be performed by mass spectrometry, which in turn presupposes a knowledge of the relevant compound's mass spectral characteristics. This is a problem for piroxicam and tenoxicam, as to date the only mass spectral data for either of these compounds or their metabolites appearing in the literature are a positive ion atmospheric pressure chemical ionisation triple quadrupole LC/MS 2 product ion spectrum of tenoxicam3 and a matrix‐assisted laser desorption/ionisation time‐of‐flight spectrum of piroxicam 4. To remedy the situation, we now report the results of an investigation into the metabolism and urinary excretion of both piroxicam and tenoxicam following oral administration to the horse and provide a variety of ion trap mass spectral data for both compounds and their major urinary metabolites under electrospray ionisation (ESI) conditions.…”

<b>Indirect spectrophotometric determination of piroxicam and tenoxicam through oxidation with potassium permanganate</b>

“…The pharmacological actions of these oxicams are related to inhibition of cyclooxygenase (Cox), a key enzyme of prostaglandine biosynthesis at the site of inflammation [1]. Several methods have been reported for determination of piroxicam and tenoxicam including spectrophotometry for PX [2][3][4][5][6][7][8][9][10] and for TX [11][12][13][14], chromatography, electroanalytical and physicochemical methods for PX [15][16][17][18][19][20] and for TX [21][22][23]. Among the various methods available for the determination of drugs, spectrophotometry continues to be very popular, because of its simplicity, specificity and low cost.…”