Citalopram and metabolites

Citalopram and metabolites Chirobiotic V MeOH/acetic acid/TEA (99.9/0.055/0.060) 272... 

Inhibition of H-monoamine uptake in rat brain synaptosomes by citalopram and metabolites [75 and refs therein]. 

Zheng, Z., Jamour, M., and Klotz, U., Stereoselective HPLC-assay for citalopram and its metabolites, Ther. Drug Monitor, 22, 219, 2000. 

Kosel M, Eap CB, Amey M, Baumann P. 1998. Analysis of citalopram and its demethylated metabolites using chiral liquid chromatography. J Chromatogr B 719 234-238. 

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. 

Two parallel groups of healthy volunteers received 20 mg of citalopram (n = 12) or placebo (n = 6) once daily for 10 d in a randomized, double-blind fashion, followed by concomitant selegiline, 10 mg once daily for 4 d. The safety of this drug combination was assessed by measurements of blood pressure, heart rate, body temperature, and inquiries for adverse events. Blood samples were taken for the analysis of serum concentrations of selegiline, citalopram, and their metabolites. In addition, plasma was obtained to measure prolactin, epinephrine, norepinephrine, and 3,4-dihydroxyphanolglycol (DHPG), the urinary excretion of norepinephrine and 5-hydroindoleacetic acid (5-HIAA), the urinary metabolite of serotonin. 

Lew authors described antidepressant analysis in alternative specimens, such as hair or oral fluid. LC-CID-MS and MS/MS mass spectra libraries for identification of several drugs were employed by Muller et al. [32] for the detection of maprotiline, citalopram, and their desmethyl metabolites in authentic hair specimens extracted ions chromatograms were employed for subsequent antidepressant quantification. Also Klys et al. [33] applied LC-MS/MS to the analysis of blood, urine, and hair specimens in a fatal case due to clomipramine overdose in combination with alcohol. Blood clomipramine and norclomipramine concentrations explained the fatal outcome, and hair analysis confirmed that the deceased was on clomipramine treatment for, at least, 12 months prior to his death. With regard to oral fluid analysis, de Castro et al. [34] developed and validated a... 

Jiang T, Rong Z, Peng L et al (2010) Simultaneous determination of citalopram and its metabolite in human plasma by LC-MS/MS applied to pharmacokinetic study. J Chromatogr B Anal Technol Biomed Life Sci 878 615-619... 

This suggests that even modest overdoses of citalopram can cause QTC prolongation and that cardiac monitoring should be considered. Based on the pharmacokinetic profile of citalopram and the temporal pattern of QTC change, the authors suggested that the effect of citalopram on the QTC interval was mediated by one of its metabolites, dimethylcitalopram. 

Several studies have examined the interaction between selective serotonin reuptake inhibitors (SSRIs) and P-gp and have shown that not all members of this class of drugs are P-gp substrates. Concentrations of paroxetine and venlafaxine/ but not fluoxetine/ were significantly increased in the brains of mdrla/b (—j—) knockout mice compared to concentrations in the wild-type mice.(100) In cell culture studies/ sertraline/ its metabolite desmethylsertraline/ and paroxetine were shown to be potent inhibitors of P-gp however/ citalopram and venlafaxine were only weak inhibitors (101/ 102). 

Arbutin, kojic acid, and hydroquinone Letrozole, citalopram and their metabolites... 

Olesen, O.V. Linnet, K. Simplified high-performance liquid chromatographic method for the determination of citalopram and desmethylcitalopram in serum without interference from commonly used psychotropic drugs and their metabolites. J.Chromatogr.B, 1996, 675, 83-88... 

The other metabolites didemethyl citalopram and citalopram-N-oxide are still 5-HT selective but much less potent compared to the main metabolite and the parent compound citalopram (table 10). Being minor metabolites these compounds will probably not contribute to the clinical effect of citalopram in contrast to Ihe main metabolite demethylcitalopram. 

Citalopram and its metabolites have a negligible inhibitory effect on the uptake of DA in rat brain synaptosomes compared to the effect on 5-HT uptake. 

Sidhu, J. Priskorn, M. Poulsen, M. Segonzac, A. Grollier, G. Larsen, F. Steady-state pharmacokinetics of the enantiomers of citalopram and its metabolites in humans. Chirality 1997, 9, 686-692. 

Foglia, J.P. Pollock, B.G. Kirshner, M.A. Rosen, J. Sweet, R. Mulsant, B. Plasma levels of citalopram enantiomers and metabolites in elderly patients. Psychopharmacol. Bull. 1997, 33, 109-112. 

In a pharmacokinetic study involving 44 adolescent patients (under 21 years of age), there was considerable inter-individual variation in serum levels of citalopram and its metabolites at all doses studied. However, smoking did appear to influence the disposition of citalopram. The clinical significance of this is unknown and more study is required. 

Figure 3 Separation of citalopram and its demethylated metabolites in a human plasma extract on a vancomycin phase. Column 4.6 mm x 15 cm stationary phase Chirobiotic V, 5 pm mobile phase methanol-acetic acid-triethylamine (99.9 0.055 0.06, v/v/v), 1 ml min detector fluorescence 240/296 nm. The structure of the drug is shown it is used as the racemate. Peaks 1, alprenolol (internal standard) 2, R- - )-didesmethylcitalopram 3, R-( - )-desmethylcitalopram 4, R- - )-citalopram 5, S-( + )-citalopram 6, S-(+ )-desmethylcitalopram. S- + )-didesmethylcitalopram is not present. (Reproduced with permission from Kosel M, Eap CB, Amey M, and Baumann P (1998) Analysis of the enantiomers of citalopram. Journal of Chromatography B 719 234.)...

The antibiotics vancomycin (shown in Table 1), teicoplanin, and ristocetin A can be bonded to silica, giving a unique class of macrocyclic glycopeptide CSPs. They can be used in the normal-phase mode with a nonpolar eluent as well as in the reversed-phase mode with an aqueous eluent. They show unique selectivity for a large number of analytes. Figure 3 gives an example with the separation of the antidepressant citalopram and its metabolites on a vancomycin CSP. 

Citalopram and four metabolites (desmethylcitalopram, citralopram IV-oxide, citalopram propionic acid, didesmethylcitalopram) were extracted from plasma and baseline resolved on a C g colunm (2 = 249 nm, ex 302 nm, em). A columnswitching setup utilized a 1 mM phosphate buffer at pH 3 application solvent and a 30/70 acetonitrile/water/water (20 mM phosphate buffer and 0.1% diethylamine at pH 3) elution solvent [1454]. Peak shapes were excellent and limits of quantitation of 2ng/mL were reported. Calibration standards fimn 2 to 150ng/mL were used. 

Duverneuil and coworkers (2003) have developed a method for the determination of 11 of the most commonly prescribed non-tricyclic antidepressants and some of their metabolites these include paroxetine, fluoxetine, norfluoxetine, sertraline, citalopram, fluvoxamine mirtazapine, venlafaxine, and 0-des-methylvenlafaxine. The method involves an LLE procedure followed by an HPLC separation with photodiode-array UV detection at three different wavelengths (220, 240, and 290 nm). The total run time was 18 min. The extraction recoveries were calculated to be in the range of 74-109% and the lower limit of detection (LLOD) reported was 2.5-5 ng/ml. A method published by Tournel and associates (2001) also reported the simultaneous determination of several newer antidepressants by RP-HPLC with UV detection. The compounds were isolated from human serum using an LLE process. The LLOQ ranged from 15-50 ng/ml depending on the analyte of interest. The total run time for all compounds eluted was approximately 20 min. 

SSRI medications differ greatly in their chemical structures and composition. For example, citalopram is a tertiary amine with 2 N-metabolites. All three com-... 

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