Theophylline assay

Matheson, L.E., Bighley, L., and Hendeles, L., Drug interferences with the Schack and Waxier plasma theophylline assay, Am. J. Hosp. Pharmacol., 34,496,1977. 

Edholm, L.E. 1980. Specific methods for theophylline assay in biological samples. Eur J Respir Dis Suppl. 109 45. 

Figure 30.13, illustrates the HPLC chromatogram of theophylline assay with four distinct peaks. 

E499 Apple, F.S., Benson, P., Abraham, P.A., Rosano, T.G. and Halstenson, C.E. (1989). Assessment of renal function by inulin clearance Comparison with creatinine clearance as determined by enzymatic methods. Clin. Chem. 35, 312-314. E500 Auslander, W. (1989). Die quantitative Analytik mit der Ektachem-Mehrschichtenfilmtechnik. Lab. med. 73, 71, Leserbrief E501 Ayers, G.J., Baldwin, A.J., Fowler, A.M., Goudie, J.H. and Burnett, D. (1989). Theophylline assay on Kodak Ektachem DTSC - Performance and interference by structurally-related compounds and salicylate. Ann. Clin. Biochem. 26, 268-273. 

E641 Koh, T., Hickey, G., Dutta, P. and Edwards, R. (1990). Performance characteristics of theophylline assay on Paramax analytical system. Clin. Chem. 36, 1040, Abstr. 413. 

Cheung, C.M. and Soldin, S.J. (1984). Clinical evaluation of theophylline assay on the Ames Seralyzer. Clin. Chem. 30, 1015, Abstr. 386. 

Busch, R.P. and Virji, M.A. (1985). Serum theophylline assay by Ames Seralyzer compared with Abbott TD, in pediatric care. Clin. Chem. 31, 1247-1248. Castellet, J., Pedromingo, A. and Delgado, A. (1985). Evaluation of the Seralyzer method for the determination of theophylline. Reunion Nacional Soc. Esp. Quimica Clin. 4, 5. 

S200 Clifton, G.D., West, M.E., Hunt, B.A. and Burki, N.K. (1988). Accuracy and time requirements for use of three rapid theophylline assay methods. Clin. Pharm. 7,462-466. 

S271 Mouine, J., Richard, L., Ribon, B., Hersant, J., Sarmini, H. and Houin, G. (1990). Methods of theophylline assay and therapeutic monitoring of this drug. Ann. Biol. Clin. 48, 287-293. 

A. Specific levels. Semm caffeine levels are not routinely available in hospital laboratories but can be determined at commercial toxicology laboratories. Toxic concentrations may be detected by cross-reaction with theophylline assays (see Table 1-33, p 44). Coffee drinkers have caffeine levels of 1-10 m L, while levels of 80 mg/L have been associated with death. The level associated with a high likelihood of seizures is unknown. 

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. 

IB parts by weight of theophylline are added to 37.8 parts by weight of aqueous choline bicarbonate (47% assay) and the mixture stirred and heated at B0°C to 90°C until the evolution... 

There are numerous methods in the literature for the determination of caffeine, theobromine, and theophylline in food matrices, including coffee, tea, and cocoa. Until recently, methods have emphasized the determination of the major methylxanthines in a commodity, for example, caffeine in coffee or theobromine in cocoa. Present methods range from being specific for one of the compounds in a single matrix to being an all-encompassing assay of major and minor methylxanthines in food products. 

HPLC allows a quantitative determination with relatively simple extractions. In many cases, extraction only involves a heating of the commodity with water, followed by filtration and injection onto an HPLC column. In the determination of caffeine, theobromine, and theophylline in cocoa, coffee, or tea, as well as in other foods, there is scarcely a month that passes without a new paper on this assay. Kreiser and Martin provide typical conditions for analysis.28 In their studies, samples were extracted in boiling water and filtered prior to injection onto the HPLC column. The HPLC conditions used a Bondapak reversed phase column and a mobile phase of water methanol acetic acid (74 25 1) with detection at 280 nm. This method is accurate, precise, and conserves time. It has also been adopted by the AOAC as an official method for the determination of theobromine and caffeine in cocoa beans and chocolate products.29... 

In the clinical area, the largest share of analytical methods development and publication has centered on the determination of theophylline in various body fluids, since theophylline is used as a bronchodilator in asthma. Monitoring serum theophylline levels is much more helpful than monitoring dosage levels.44 Interest in the assay of other methylxanthines and their metabolites has been on the increase, as evidenced by the citations in the literature with a focus on the analysis of various xanthines and methylxanthines. 

Hill, R.E., Retention behavior of a bonded reversed phase in high performance liquid chromatographic assay of serum theophylline, J. Chromatogr., 135,419,1977. 

Monodisperse microspheres imprinted with theophylline or 17 (3-estradiol were used in competitive radioimmunoassays showing the MIP s high selectivity for the template molecule. In this case the assay is based on the competition of the target molecule with its radioactively labeled analogue for a limited number of antibody binding sites [77,118]. Figure 15 demonstrates that displacing the radioactively marked theophylline from the imprinted polymer was only possible with theophylline as competitor. Structurally related molecules showed effects solely at elevated concentrations [77]. 

A variety of xanthines including caffeine, theobromine, and theophylline have been found from food materials including.coffee, chocolate, and tea (419-420). Theophylline determination in sera has been much studied. The technique allows the determination of theophylline at serum levels of 1.5-20 mg/liter theophylline with sample sizes ranging from 50 to 10 /xl (42 -425). Hill (426) assayed theophylline using 50 /xl of serum and an analysis time of 8 min with good interbatch precision and accuracy. Alternative methods which allow the determination of as little as 0.1 mg/ml (427) or 20 ng theophylline in 10 ml serum have been described (428). 

Figure 15.6 Comparison of the values measured by an enzyme-multiplied immunoassay technique (EMIT) assay and a molecularly imprinted sorbent assay (MIA) for determination of theophylline in 32 patient serum samples. The correlation coefficient was 0.98. Reprinted from Vlatakis et al. (1993). Copyright 1993 Macmillan Ltd.

Though better tolerated, significantly less bronchodilating activity vs theophylline. Serious dosing errors possible if dyphylline monitored with theophylline serum assays... 

Blood samples were taken at 0.25, 0.5, 1.5, 2.5, 4.5, 6.5, 8.5, 10.5 and 12.5 h and the concentration of theophylline in serum was assayed by a spectrophotometric method [7]. The samples were analysed in duplicate. Bioavailability was calculated from the area under the concentration curve following the trapezoidal rule. 

Some work has demonstrated that pulse voltammetry at the carbon paste electrode can be applied to the assay of drugs in body fluids [197,198]. Methods based on the electrooxidation of theophylline [197] and acetaminophen [198] were described at concentrations of approximately 5-10 fxg/mL plasma. 

The Mosbach group described in 1993 the first assay in which polymers imprinted with either theophylline or diazepam replaced antibodies in competitive RILA... 

Renger, B., Jehle, H., Fischer, M., and Funk, W. Validation of analytical procedures in pharmaceutical analytical chemistry HPTLC assay of theophylline in an effervescent tablet. J Planar Chrom 8 269-278 (July/Aug. 1995). 

LAI E P C, FARFARA A, VANDERNOOT V A, KONO M and POLSKY B (1998), Surface plasmon resonance sensors using molecularly imprinted polymers for sorbent assay theophylline, caffeine and xanthan , Can J Chem, 76, 265. 

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