Theophylline determination

Ultraviolet spectroscopy is used in many clinical laboratories due to its ease of operation and availability. A classical method for theophylline determination in plasma is the one of Schack and Waxier.45 The original method had interferences from phenobarbitol and various xanthine derivatives such as theobromine.46 The modification of the method by Jatlow47 eliminated the interferences from barbituates but included the various... 

Pranskevich, C.A., Swihart, J.I., and Thoma, J.J., Serum theophylline determination.by isothermal gas-liquid chromatography on 3% SP2250-DB, J. Anal. Toxicol., 2,3,1978. 

T. M. Li, J. L. Benovic, and J. F. Burd, Serum theophylline determination by fluorescence polarization im+munoassay utilizing an umbelliferone derivative as a fluorescent label, Anal. Biochem. 118, 102-107 (1981). 

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). 

Haga et al. developed another type of immunosensor by combining an enzyme membrane immunoassay and an enzyme sensor using oxygen electrodes (HI). In this assay antigen molecules (theophylline) are attached on the surface of the liposomes and an enzyme (horseradish peroxidase) is encapsulated in the sensitized liposome. When antibody (antitheophylline antibody) and complement are added, the enzyme is released by the liposome lysis. The enzyme activity with the NADH-NAD reaction can be determined by the oxygen electrode. When antigen is added, it competitively binds to antibodies, then liposome lysis and enzyme activity are decreased. The sensitivity of this method for theophylline determination was reported as 0.7 ng/ml. 

Chiem NH, Harrison DJ. Microchip systems for immunoassay an integrated im-munoreactor with electrophoretic separation for serum theophylline determination. Clin Chem 1998 44 591-598. 

Cummins IJI, Kozak PP, GiUman SA. Theophylline determinations. Ann Allergy (1976) 37,... 

Serum Theophylline Determination by Isothermal Gas-Liquid Chromatography on 3% SP2250-DB J. Anal. Toxicol. 2(1) 3-6 (1978) ... 

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. 

Enzyme immunosensors are employed for the determination of Hepatitis B surface antigen, IgG, alpha-fetoprotein, estradiol, theophylline, insulin [9004-10-8] and alburnin (69,70). However, these immunosensors generally have slow response times and slow reversibiUty (57). 

Ms. Smith, age 68 years, returned to the clinic for a follow-up visit after receiving a diagnosis of COPD. She is taking theophylline daily and using a metered-dose inhaler 4 times a day. Determine what assessments would be most important for you to make at this time. 

Catalase has also been used as an enzyme label in competitive heterogeneous enzyme immunoassays. Catalase generates oxygen from hydrogen peroxide with the oxygen determined amperometrically with an oxygen electrode. This approach has been demonstrated for a-fetoprotein theophylline and human serum albumin... 

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. 

Hieda et al. determined theophylline, theobromine, and caffeine in human plasma and urine by gradient capillary HPLC with frit fast atom bombardment (FAB) mass spectrometry with 7-ethyl theophylline as the internal standard.64... 

The determination of theophylline in plasma can also be accomplished by various immunoassay techniques.66-67 Theophylline was also determined by a polarization fluoroimmunoassays but found to have a caffeine interference.88. In a more research oriented application, the interaction of caffeine with L-tryptophan was studied using h NMR with the results indicating that caffeine interacted with tryptophan in a 1 1 molar ratio through parallel stacking.69... 

Schack, J.A. and Waxier, S.H., Ultraviolet spectrophotometric method for the determination of theophylline and theobromine in blood and tissues, J. Pharmacol. Exp. Ther., 97,283,1949. 

Gupta, R.C. and Lundberg, G.D., Qualitative determination of theophylline in blood by differential spectrophotometry, Anal Chem., 45,2402,1973. 

Peng, G.W., Gadalia, M.A.F., and Chiou, W.L., High performance liquid chromatographic determination of theophylline in plasma, Clin. Chem., 24,357,1978. 

Sommadossi, J.P., Aubert, C., Cano, J.P., Durand, A., and Viala, A., Determination of theophylline in plasma by high performance liquid chromatography, J Liquid Chromatogr., 4,97,1981. 

Hieda, Y., Kashimura, S., Hara, K., and Kageura, M., Highly sensitive and rapid determination of theophylline, theobromine and caffeine in human plasma and urine by high performance liquid chromatography frit fast atom bombardment spectrometry, J. Chromatogr., 667,241,1995... 

Koup, J.R. and Brodsky, B., Comparison of homogeneous enzyme immunoassay and high pressure liquid chromatography for the determination of theophylline concentration in serum, Am. Rev. Respir. Dis., 117,1135,1978. 

Oellerich, M., Klupmann, W.R., Beneking, M., Sybrecht, G.W., Staib, A.H., and Schuster, R., Determination of theophylline in serum by nonisotopic immunoassays (EMIT, SLFIA, NIIA) and HPLC-CA comparative study, Fresenius Z. Anal. Chem., 311,355,1982. 

Terada, H., Sakabe, Y., High performance liquid chromatographic determination of theobromine, theophylline and caffeine in food products, J. Chromat., 291, 453, 1984. 

Drug Release from PHEMA-l-PIB Networks. Amphiphilic networks due to their distinct microphase separated hydrophobic-hydrophilic domain structure posses potential for biomedical applications. Similar microphase separated materials such as poly(HEMA- -styrene-6-HEMA), poly(HEMA-6-dimethylsiloxane- -HEMA), and poly(HEMA-6-butadiene- -HEMA) triblock copolymers have demonstrated better antithromogenic properties to any of the respective homopolymers (5-S). Amphiphilic networks are speculated to demonstrate better biocompatibility than either PIB or PHEMA because of their hydrophilic-hydrophobic microdomain structure. These unique structures may also be useful as swellable drug delivery matrices for both hydrophilic and lipophilic drugs due to their amphiphilic nature. Preliminary experiments with theophylline as a model for a water soluble drug were conducted to determine the release characteristics of the system. Experiments with lipophilic drugs are the subject of ongoing research. 

In a further application of MI-SPE, theophylline could be separated from the structurally related caffeine by combining the specific extraction with pulsed elution, resulting in sharp baseline-separated peaks, which on the other hand was not possible when a theophylline imprinted polymer was used as stationary phase for HPLC. A detection limit of 120 ng mb1 was obtained, corresponding to a mass detection limit of only 2.4 ng [45]. This combination of techniques was also used for the determination of nicotine in tobacco. Nicotine is the main alkaloid in tobacco and is the focus of intensive HPLC or GC analyses due to its health risk to active and passive consumers. However, HPLC- and GC-techniques are time-consuming as well as expensive, due to the necessary pre-purification steps required because the sample matrices typically contain many other organic compounds besides nicotine. However, a simple pre-concentration step based on MI-SPE did allow faster determination of nicotine in tobacco samples. Mullett et al. obtained a detection limit of 1.8 jig ml 1 and a mass detection limit of 8.45 ng [95]. All these examples demonstrate the high potential of MI-SPE to become a broadly applicable sample pre-purification tool. 

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