Metabolite in plasma

Alkaloids, e.g. laubasine and its metabolites in plasma, urine and bile... 

Recent applications of HPAEC-PAD are many and varied. A representative list includes quantitation of polyglucose metabolites in plasma of dialysis patients,148 analysis of heat-treated milk,149 carbohydrate content in lipopolysaccharides,150 phosphorylated sugars in tissue samples,151 composition of soybean meal,152 carbohydrate composition of recombinant modified tissue plasminogen activator,153 analysis of cyclization products from an enzyme reaction,154 carbohydrate content of glycoconjugate vaccines,155 and monitoring of patients with rheumatoid arthritis.156... 

Burke, R. A., Hvizd, M. G., and Shockley, T. R., Direct determination of polyglucose metabolites in plasma using anion-exchange chromatography with pulsed amperometric detection, ]. Chromatogr. B, 693, 353, 1997. 

HPLC coupled to MS was used for the determination of dimethyl xanthine metabolites in plasma.82 There have also been a number of methods published on the use of HPLC with a PDA detector. In 1996, Mei published a method for the determination of adenosine, inosine, hypoxanthine, xanthine, and uric acid in microdialysis samples using microbore column HPLC with a PDA detector.63 In this method, samples were directly injected onto the HPLC without the need for any additional sample treatment. 

As part of new drug discovery, the trend toward screening for metabolites in plasma samples being assayed for the dosed compound (NCE) is increasing. This effort is sometimes called metabolite profiling116 and it is important for two reasons (1) for compounds with low bioavailability due to extensive metabolism, metabolites may help medicinal chemists learn to modify the NCE to block... 

Souverian S. et al., 2003. Rapid analysis of fluoxetine and its metabolite in plasma by LC-MS with columnswitching approach. Anal Bioanal Chem 377 880. 

Zell M., Husser C., and Hopfgartner G., 1997b. Column-switching high-performance liquid chromatography combined with ionspray tandem mass spectrometry for the simultaneous determination of the platelet inhibitor Ro 44-3888 and its pro-drug and precursor metabolite in plasma. J Mass Spectrom 32 23. 

De la Torre, R. et al. 1998. Quantitative determination of tricyclic antidepressnts and their metabolites in plasma by solid phase extraction (bond-elut TCA) and separation by capillary gas chromatography with nitrogen-phosphorus detection. Ther Drug Monit. 20 340. 

Andersen, A., Warren, D J., and Slordal, L. 1993. A sensitive and simple high performance liquid chromatographic method for the determination of doxorubicin and its metabolites in plasma. Ther Drug Monit. 15 455. 

Tetraplatin (11.177) is another dach derivative, one that belongs to the subclass of lVv complexes. In water, Cl is displaced by H20, with equilibrium at ca. 70% of the initial concentration being reached in 1 h at 25° [189], In 0.9% NaCl solution, no Cl- displacement was observed. In plasma, tetraplatin undergoes rapid reduction to [PtCl2(dach)] (11.178), and reactivity toward plasma proteins is comparable to that of oxaliplatin [195], Thus, both oxaliplatin and tetraplatin yield the same major metabolite in plasma, which might account for their similar cytotoxicity [197]. 

Cheung SW, Tang SW, Remington G. 1991. Simultaneous quantitation of loxapine, amoxapine and their 7- and 8-hydroxy metabolites in plasma by high-performance liquid chromatography. J Chromatogr 564(1) 213-221. 

Foglia JP, Sorisio D, Kirshner MA, Mulsant BH, Perel JM. 1995. Quantitative determination of perphenazine and its metabolites in plasma by high-performance liquid chromatography and coulometric detection. J Chromatogr B Biomed Appl 668(2) 291-297. 

He H, Shay SD, Caraco Y, Wood M, Wood AJ. 1998. Simultaneous determination of codeine and its seven metabolites in plasma and urine by high-performance liquid chromatography with ultraviolet and electrochemical detection. J Chromatogr B Biomed Sci Appl 708(1-2) 185-193. 

Hue B, Palomba B, Giacardy-Paty M, Bottai T, Alric R, et al. 1998. Concurrent high-performance liquid chromatographic measurement of loxapine and amoxapine and of their hydroxylated metabolites in plasma. Ther Drug Monit 20(3) 335-339. 

Pirola R, Mundo E, BeUodi L, Bareggi SR. 2002. Simultaneous determination of clomipramine and its desmethyl and hydroxy metabolites in plasma of patients by high-performance liquid chromatography after solid-phase extraction. J Chromatogr B 772(2) 205-210. 

Queroz RH, Lanchote VL, Bonato PS, de Carvaldo D. 1995. Simultaneous HPLC analysis of tricyclic antidepressants and metabolites in plasma samples. Pharm Acta Helv 70 (2) 181-186. 

Vanapalli SR, Kambhampati SP, Putcha L, Bourne DW. 2001. A liquid chromatographic method for the simultaneous determination of promethazine and three of its metabolites in plasma using electrochemical and UV detectors. J Chro-... 

Kratzsch C, Peters FT, Kraemer T, Weber AA, Maurer HH. 2003. Screening, library-assisted identification and validated quantification of fifteen neuroleptics and three of their metabolites in plasma by liquid chromatography/ mass spectrometry with atmospheric pressure chemical ionization. J Mass Spectrom 38 283. 

Another important feature of HILIC is the improved sensitivity with electrospray mass spectrometry. At least one order of magnitude, but often more, can be gained compared with reversed-phase separations. This is significant for the analysis of parent drugs and metabolites in plasma or urine samples. Together with the ability to retain very polar metabolites, this feature makes HILIC now a very attractive technique in pharmacokinetics. In addition, HILIC can be combined conveniently... 

CH 10 METABOLISM OF AMMONIA AND NUCLEIC ACIDS Table 10.5 Changes in the concentration of various intermediates of the urea cycle or their metabolites in plasma or urine in various enzyme deficiency diseases in humans ... 

Hsieh, Y. Brisson, J. M. Wang, G. Ng, K. Korfmacher, W. A. Simultaneous fast HPLC-MS/MS analysis of drug candidates and hydroxyl metabolites in plasma. 

Li, A. C. Alton, D. Bryant, M. S. Shou, W. Z. Simultaneously quantifying parent drugs and screening for metabolites in plasma pharmacokinetic samples using selected reaction monitoring information-dependent acquisition on a QTrap instrument. Rupid Commun Mass Spectrom 2005, 19, 1943-1950. 

Figure 8. Plasma disposition of sulfadimidine (SDM), its 6-methylhydroxy (CH2OH), 5-hydroxy (SOH) and N -acetyl (N ) metabolites in plasma of a laying-hen during and after cessation of multiple oral dosing of 100 mg SDM/kg/day during 5 days ...

In addition to the pharmacokinetics of the drug, the first study in man can provide important information about its metabolites. If assay methodology has been developed, metabolites in plasma can be detected and the AUCs and half-lives determined. Further information can be obtained from assaying urine for drug and, if possible, metabolites. Renal clearance can be calculated over time intervals and the ratio of... 

Cl 5. Curry, S. H., Determination of nanogram quantities of chlorpromazine and some of its metabolites in plasma using ga.s-liquid chromatography with an electron capture detector. Anal. Chetn. 41, 1251-1256 (1968). 

Renai/Hepatic function impairment The safety and pharmacokinetics of rimantadine in renal and hepatic insufficiency only have been evaluated after single dose administration. In a single dose study of patients with anuric renal failure, the apparent clearance was approximately 40% lower and the elimination half-life was 1.6-fold greater than that in healthy controls. In a study of 14 people with chronic liver disease (mostly stabilized cirrhotics), no alterations in the pharmacokinetics were observed after a single dose of rimantadine. However, the apparent clearance of rimantadine following a single dose to 10 patients with severe liver dysfunction was 50% lower than that reported for healthy subjects. Because of the potential for accumulation of rimantadine and its metabolites in plasma, exercise caution when patients with renal or hepatic insufficiency are treated with rimantadine. 

After a single 80 mg oral dose of isotretinoin to 74 healthy adult subjects, concurrent administration of food increased the extent of formation of all metabolites in plasma when compared with the extent of formation under fasted conditions. 

Dai, G., Wei, X., Liu, Z., Liu, S., Marcucci, G., and Chan, K. K., Characterization and quantification of Bcl-2 antisense G3139 and metabolites in plasma and urine by ion-pair reversed phase HPLC coupled with electrospray ion-trap mass spectrometry. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences 825(2), 201-213, 2005. 

Fernandez et al. [27] applied HPLC with diode array detection (DAD) to the determination of heroin, methadone, cocaine and metabolites in plasma after mixed-mode SPE. Analytes were separated using a RP8 column (250 mm x 4.6 mm i.d., 5 jam particle size) and acetonitrile-phosphate buffer pH 6.53 as mobile phase with elution in the gradient mode. The method, which provides a LLOQ of 0.1 j,g/mL for all compounds, was successfully applied to 21 plasma samples from fatal overdoses. 

A fully automated on-line SPE-HPLC-MS-MS method was developed and validated for the direct analysis of 14 antidepressants and their metabolites in plasma by de Castro et al. [75]. After direct injection of 50pL of plasma without prior sample pre-treatment, gradient RP separation was completed in 14 min, with a sample throughput of 3h. LOQs were estimated to be at 10 ng/ mL. Analytes proved to be stable during sample process with the exception of clomipramine and norclomipramine. 

A radioimmunoassay method has been reported for the monitoring of therapeutic concentration of chlorpromazine and its 7-hydroxy metabolite in plasma by [184]. The limit of detection for chlorpromazine was reported to be 0.1 ng, and its calibration curve linear up to 2 ng. The limits of detection for the 7-hydroxy metabolite was reported as 0.1 ng, and the calibration curve linear up to 1.2 ng. 

Rochat, B., Amey, M., and Baumann, P. (1995a) Analysis of enantiomers of citalopram and its demethylated metabolites in plasma of depressive patients using chiral reverse-phase liquid chromatography. Ther Drug Monit 17 273-279. 

Data for the metabolites in plasma are generally for the unbound forms, but there is ample evidence that PPT bind noncovalently to proteins. Most studies on PPT-protein interaction have focused on protein utilization or astringency but a few studies have addressed binding to plasma proteins and lipoproteins. " " Strongest binding has been associated with 1,2-dihydroxyphenols and proline-rich proteins such as those character-istic of human saliva and structure-activity relationships have been reported. 

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