J Chromatogr B Biomed Appl. 1995 Apr 7;666(1):117-26.
Development and comparison of high-performance liquid chromatographic methods with tandem mass spectrometric and ultraviolet absorbance detection for the determination of cyclobenzaprine in human plasma and urine.

Constanzer M, Chavez C, Matuszewski B.

Merck Research Laboratories, West Point, PA 19486, USA.

Sensitive assays for the determination of cyclobenzaprine (I) in human plasma and urine were developed utilizing high-performance liquid chromatography (HPLC) with tandem mass spectrometric (MS-MS) and ultraviolet (UV) absorbance detections. These two analytical techniques were evaluated for reliability and sensitivity, and applied to support pharmacokinetic studies. Both methods employed a liquid-liquid extraction of the compound from basified biological sample. The organic extract was evaporated to dryness, the residue was reconstituted in the mobile phase and injected onto the HPLC system. The HPLC assay with MS-MS detection was performed on a PE Sciex API III tandem mass spectrometer using the heated nebulizer interface. Multiple reaction monitoring using the parent-->daughter ion combinations of m/z 276 --> 215 and 296 --> 208 was used to quantitate I an internal standard (II), respectively. The HPLC-MS-MS and HPLC-UV assays were validated in human plasma in the concentration range 0.1-50 ng/ml and 0.5-50 ng/ml, respectively. In urine, both methods were validated in the concentration range 10-1000 ng/ml. The precision of the assays, as expressed as coefficients of variation (C.V.) was less than 10% over the entire concentration range, with adequate assay specificity and accuracy. In addition to better sensitivity, the HPLC-MS-MS assay was more efficient and allowed analysis of more biological fluid samples in a single working day than the HPLC-UV method.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7655609&dopt=Abstract cyclobenzaprine Flexeril





J Chromatogr Sci. 1995 Jun;33(6):297-302.
Microbore liquid chromatography of tertiary amine anticholinergic pharmaceuticals with tris(2,2'-bipyridine)ruthenium(III) chemiluminescence detection.

Holeman JA, Danielson ND.

Department of Chemistry, Miami University, Oxford, Ohio 45056, USA.

The post-column chemiluminescent reaction of six anticholinergic alkaloid compounds with tris(2,2'-bipyridine)ruthenium(III) (Ru(bpy)3(3+)) is applied to microbore high-performance liquid chromatography (HPLC). At flow rates less than 200 microL/min, the capillary mixing cell in which Ru(bpy)3(3+) and the analyte are mixed directly allows for good light detection. In contrast, a diminished signal occurs at these low flow rates with conventional post-column mixing in a tee. Optimal chemiluminescent pH conditions for atropine, scopolamine, dicyclomine, cyclopentolate, cyclobenzaprine, and procyclidine are determined at moderately basic conditions (pH 7 to 9). 2-Butanone is found to be compatible with the chemiluminescent reaction, whereas tetrahydrofuran and propionitrile cause an increase in background noise and a chemiluminescent signal loss. As 2-butanone is more nonpolar than acetonitrile, it assists in the elution of these hydrophobic anticholinergic compounds. Five anticholinergic compounds are resolved successfully with a PRP-1 polymeric column and a slightly basic mobile phase, but a C8 silica column is better suited for the more hydrophobic compounds (cyclobenzaprine, procyclidine, and dicyclomine).

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Clin Rheumatol. 1994 Mar;13(1):88-9.
Fibromyalgia associated with female urethral syndrome.

Paira SO.

Department of Internal Medicine, Hospital Jose M. Cullen, Santa Fe, Argentina.

Thirty-eight out of 212 patients (18%) with fibromyalgia met the criteria for the definition of female urethral syndrome (FUS). None of the patients from the control group met these criteria. The treatment for FUS was the same as that for fibromyalgia: cyclobenzaprine or diazepam and nonsteroidal anti-inflammatory drugs with a partial response in both pathologies. We should consider FUS in the evaluation of every patient with fibromyalgia.

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Chem Pharm Bull (Tokyo). 1993 Nov;41(11):1987-93.
Study on zwitter-ionization of drugs. II. Synthesis and pharmacological activity of some N-[3-(5H-dibenzo[a, d]cyclohepten-5-ylidene) propyl]-N-methylamino- and N-[3-(6H-dibenz[b, e]oxepin-11-ylidene) propyl]-N-methylamino-alkanoic acid derivatives and related compounds.

Muramatsu H, Sawanishi H, Iwasaki N, Kakiuchi M, Ohashi T, Kato H, Ito Y.

First Division of the Research Laboratory for Development of Medicine, Hokuriku University, Ishikawa, Japan.

A series of N-[3-(5H-dibenzo[a, d]cyclohepten-5-ylidene)propyl]-N-methylamino- (6a) and N-[3-(6H-dibenz-[b, e]oxepin-11-ylidene)propyl]-N-methylamino-alkanoic acid derivatives (6b) and related compounds (6c-f) were synthesized and examined for pharmacological activities in vitro, i.e., inhibitory effect on monoamine [noradrenaline (NA) and 5-hydroxytryptamine (5-HT)] uptake, inhibitory effect on 5-HT-, histamine-, acetylcholine- and NA-induced contraction, and binding affinity for alpha 2-adrenoceptor and dopamine D2-receptor. In vitro tests indicated that zwitter-ionization was capable of maintaining H1-antihistaminic activity while greatly reducing other pharmacological activities. Further, 6a-f showed much stronger inhibitory effects on compound 48/80-induced lethality in rats than did the corresponding N,N-dimethylamines (2a-f). 3-[N-[3-(6H-Dibenz[b, e]oxepin-11-ylidene)propyl]-N-methylamino]- propionic acid (6b-2), selected as a candidate antiallergic agent of a new type, equally potent in rats and guinea-pigs, exhibited strong inhibitory effects on 48 h homologous passive cutaneous anaphylaxis (PCA) in rats (ED50 = 0.019 mg/kg, p.o.) and on histamine-induced bronchoconstriction in anesthetized guinea-pigs (ED50 = 0.0067 mg/kg, p.o.).

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8293521&dopt=Abstract cyclobenzaprine Flexeril