J Pharm Sci. 1976 Jun;65(6):815-21.
Identification of 10, 11-epoxide and other cyclobenzaprine metabolites isolated from rat urine.

Belvedere G, Pantarotto C, Rovei V, Frigerio A.

Cyclobenzaprine [Flexeril] (40 mg/kg ip) was administered to rats, and six urinary metabolites of this drug were identified. They were the 10, 11-epoxide, the N -oxide, the desmethyl derivative, the hydroxylated and desmethylhydroxylated compounds, and the N-oxide hydroxylated at the 10- or 11-position. Mass spectrometric analysis confirmed their structures.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=932964&dopt=Abstract cyclobenzaprine Flexeril





J Anal Toxicol. 1998 Sep;22(5):374-82.
Isotope dilution gas chromatographic-mass spectrometric measurement of tricyclic antidepressant drugs. Utility of the 4-carbethoxyhexafluorobutyryl derivatives of secondary amines.

Way BA, Stickle D, Mitchell ME, Koenig JW, Turk J.

Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

Stable isotope dilution gas chromatographic-mass spectrometric (GC-MS) measurement of tricyclic antidepressants (TCA) is a useful alternative to high-performance liquid chromatography (HPLC) methods when interfering substances prevent accurate quantitation by HPLC. For satisfactory GC-MS analysis, secondary amine TCA must be derivatized. Commonly employed trifluoroacetyl and heptafluorobutyryl derivatives are relatively unstable and cause rapid deterioration of capillary GC columns. Therefore we examined 4-carbethoxyhexafluorobutyryl chloride (CHFB-CI) as an alternative derivatizing agent and developed a stable isotope dilution GC-MS method employing ring-labeled [2H4]-desipramine and [2H4]-imipramine internal standards, which permits measurement of desipramine, nortriptyline, imipramine, and amitriptyline in plasma samples containing one or all of these analytes. The GC-MS assay is linear for each analyte from the lower limit of quantitation (25 ng/mL) up to 1500 ng/mL and correlates well with HPLC measurements. The GC-MS analytic coefficient of variation was 9.7 +/- 1.3% for all analytes considered together. Although interferences are observed in the HPLC assay, thioridazine, perphenazine, cyclobenzaprine, and norcyclobenzaprine do not interfere with GC-MS measurements of the TCA examined here. The stability of the CHFB derivative of secondary amine TCA was found to be superior to that of the trifluoroacetyl derivatives of these compounds.

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J Pharm Sci. 1976 Aug;65(8):1253-5.
GLC determination of cyclobenzaprine in plasma and urine.

Hucker HB, Stauffer SC.

A GLC determination of cyclobenzaprine in human plasma and urine is described. After extraction from alkalinized samples with heptane-isopentyl alcohol (97:3), the drug and internal standard were back-extracted into 0.1 N HCl and then reextracted into ether. Use of a lower homolog of the drug as an internal standard was effective in reducing variability. Drug concentrations as low as 25 ng/ml could be assayed with high precision. Plasma levels in humans given 40 mg po or iv ranged from 5 to 51 ng/ml; little unchanged cyclobenzaprine was present in the urine. The N-desmethyl analog of the drug was detected as a metabolite in urine.

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Xenobiotica. 1976 Oct;6(10):593-8.
Activity of liver microsomal mono-oxygenases on some epoxide-forming cyclic tricyclic drugs. I. Kinetics in vitro.

Pachecka J, Salmona M, Cantoni L, Mussini E, Pantarotto C, Frigerio A, Belvedere G.

1. The mono-oxygenase activity that forms epoxides has been studied in rat liver microsomes using as substrates carbamazepine and cyclobenzaprine, tricyclic drugs which form stable epoxides in vivo and in vitro. 2. A simple gas chromatographic method has been used to determine the amount of epoxide formed and the linearity of the enzymic reaction with time and protein concentration has been demonstrated. 3. Pre-treatment with carbamazepine increases the rate of formation of carbamazepine epoxide in rat liver microsomal preparations. 4. The effect of SKF 525-A on the formation of these epoxides has been studied.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=983116&dopt=Abstract cyclobenzaprine Flexeril