Cimetidine assay

The development of easy-to-use assays for determining theophylline blood levels afforded a handle on maintenance of effective but nontoxic levels. The relatively good availabihty of such assays in the United States probably contributed to the historical preference for theophylline treatment by U.S. physicians. Careful titration of the dose must be done on a patient-by-patient basis because individual rates of metaboHsm vary widely. Most ( 85%) of an oral dose of theophylline is metabolized by Hver microsomal enzymes. As a result many dmgs, eg, cimetidine [51481-61-9], anticonvulsants, or conditions, eg, fever, cigarette smoking, Hver disease, which affect Hver function alter theophylline blood levels. 

The assay used throughout the development of cimetidine was an animal assay on anesthetized rats. The rats were treated with histamine (11.36) to stimulate acid secretion. The same rats were then treated with a potential antagonist. Increases in stomach pH caused by administration of the antagonist were monitored to screen for activity. 

Cimetidine may be assayed in blood, urine, plasma,29 30,31,32,33,38 bile, pancreatic fluid, gastric... 

Measurement of underivatized propranolol enantiomers in serum using a celluIose-tris(3,5-dimethylphenylcarbamate) high performance liquid chromatographic (HPLC) chiral stationary phase" (54). A method for the direct measurement of the enantiomers of propranolol in human serum was developed using the OD CSP and a mobile phase composed of hexane 2-propranol W,W-dimethyloctylamine (92 8 0.01, v/v/ v). The assay was validated for use in pharmacokinetic and metabolic studies and was subsequently used in the investigation of the effect of cimetidine on the metallism and clearance of propranolol enantiomers (60). 

In 1987, Chasseur assayed cimetidine granules. This was the first reported use of a synthetically produced extended range for calibration calibration samples were produced with a range of content from 70 to 130% of label. In 1987, Osbomet used NIR to assay for nicotinamide in vitamin premixes. 

In 1987, Chasseur assayed cimetidine (CIM) granules [75], Individual batches of granules were prepared with CIM concentrations ranging from 70 to 130% of labeled potency. For calibration, first- and second-derivative spectra and one or two wavelengths were included in the model. A two-wave-length model using first-derivative spectra gave optimal results, with a SEP = 1.75%. The SEE was 2.73% for the NIR and 2.97% for UV. 

Nitsche, V. Mascher, H. New rapid assay of cimetidine in human plasma by reversed-phase high-performance liquid chromatography. J.Chromatogr., 1983, 273, 449-452... 

Abdel-Rahim, M. Ezra, D. Peck, C. Lazar, J. Liquid-chromatographic assay of cimetidine in plasma and gastric fluid. Clin.Chem., 1985, 31, 621-623... 

Tracqui, A. Kintz, P. Mangin, P Lugnier, AA. Chaumont, A.J. A new rapid HPLC assay for the simultaneous determination of two histamine H2-receptor antagonists, cimetidine and ranitidine, in human plasma. J.Toxicol.Clin.Exp., 1988, 8, 387-394 [LOD 25 ng/mL plasma]... 

Fleitman, J. Torosian, G. Perrin, J.H. Improved high-performance liquid chromatographic assay for cimetidine using ranitidine as an internal standard. J.Chromatogr., 1982, 229, 255-258 [plasma ranitidine (IS) LOD 50 ng/mL]... 

Kunitani, M.G. Johnson, D.A. Upton, R.A. Riegelman, S. Convenient and sensitive high-performance liquid chromatography assay for cimetidine in plasma or urine. J.Chromatogr., 1981, 224, 156-161 [plasma urine non-interfering acebutolol, caffeine, ketoprofen, naproxen, theophylline pharmacokinetics LOQ 100 ng/mL]... 

These researchers also compared the performance of NIR with the UV reference method in the determination of cimetidine content. Samples of 100% label strength were prepared and analyzed by both methods. The standard errors for the NIR (2.73%) and the UV (2.97%) assays were virtually identical. 

Chasseur, J.C., On-line assay of cimetidine granules by near infrared reflectance spectroscopy. Chim. Oggi, 6 21-24 (1987). 

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