Analysis of Enantiomers of Citalopram and Its Demethylated Metabolites in Plasma of Depressive Patients Using Chiral Reverse-Phase Liquid Chromatography

Rochat, Bertrand; Amey, M.; Baumann, Pierre

doi:10.1097/00007691-199506000-00011

Cited by 114 publications

(75 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This result opposites the human studies, where the S/R DCIT ratios were somewhat higher than the S/R CIT ratios (Foglia et al, 1997;Rochat et al, 1995a, b;Sidhu et al, 1997;Zheng et al, 2000). Surprisingly, the serum S/R DCIT ratios in the CIT-20 rats were much lower than the serum S/R CIT ratios (0.37 versus 0.83).…”

Section: Discussionmentioning

confidence: 57%

“…The S/R ratios of CIT from the groups treated with clinical doses of CIT (i.e. the CIT-10 and CIT-20 groups) can also be compared with S/R CIT ratios from human studies (Foglia et al, 1997;Rochat et al, 1995a, b;Sidhu et al, 1997;Zheng et al, 2000). Our data were not in complete agreement with these studies, where the mean S/R CIT ratios were found in the 0.5 ± 0.7 interval, indicating that the R-enantiomer of CIT was present in higher proportion compared with our data.…”

Section: Discussionmentioning

confidence: 99%

“…based technique as described previously (Rochat et al, 1995a) with some modi®cations. The chiral separations of CIT, DCIT, and DDCIT were optimized by response surface methodology (Carlsson & Norlander, 2001).…”

Section: Determination Of the S/r Ratios For The Enantiomers Of Citalmentioning

confidence: 99%

See 2 more Smart Citations

In vivo steady‐state pharmacokinetic outcome following clinical and toxic doses of racemic citalopram to rats

Kugelberg

Apelqvist

Carlsson

et al. 2001

British J Pharmacology

View full text Add to dashboard Cite

1 The thymoleptic drug citalopram (CIT) belongs to the selective serotonin reuptake inhibitors (SSRIs) and is today extensively used in psychiatry. Further clari®cation of the enantiomer-selective distribution of racemic CIT in both clinical and toxic doses is highly warranted. 2 By a steady-state in vivo paradigm, rats underwent chronic systemic exposure for 10 days by using osmotic pumps and the total as well as the individual distributions of the S-and Renantiomers of CIT, and its metabolites in serum and two di erent brain regions, were analysed. 3 In serum, the S/R ratios in the groups treated with 10, 20, or 100 mg kg 71 day 71 were 0.94, 0.83, and 0.34, respectively. The ratios were almost the same in the brain regions. 4 In the group treated with 100 mg kg 71 day 71 , the serum and brain total CIT levels were found to be 20 times and 6 ± 8 times higher than in the rats treated with 10 or 20 mg kg 71 day 71 , respectively. In all groups, the CIT levels were higher in brain tissue as compared to serum. 5 In a spontaneous open-®eld behavioural test, a correlation between clinical and toxic drug concentrations was observed. 6 In conclusion, the R-enantiomer was present in an increased proportion compared with the Senantiomer when higher steady-state CIT concentration was prevailing. This is of particular interest, since the S-enantiomer is responsible for the inhibition of serotonin reuptake in vitro. The present data may be of importance, as full understanding on where di erent racemic or enantiomeric drug e ects of CIT and its main metabolites are unravelled.

show abstract

Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

In vivo steady‐state pharmacokinetic outcome following clinical and toxic doses of racemic citalopram to rats

Kugelberg

Apelqvist

Carlsson

et al. 2001

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…The concentrations of the S-and R-enantiomers of citalopram, demethylcitalopram (dmcitalopram), and didemethylcitalopram (ddm-citalopram) in serum (nmol/l) and brain homogenate supernatant (pmol/g ≈ nmol/l) were determined by using HPLC with fluorescence detection as described previously (Rochat et al, 1995) with some modifications Kugelberg et al, 2001) ng/ml) for dm-citalopram and 1.7-67 nmol/l (0.5-20 ng/ml) for ddm-citalopram. The absolute recoveries from spiked drug-free plasma were between 87 and 110% ).…”

Section: Drug Concentration Determinationmentioning

confidence: 99%

Altered brain concentrations of citalopram and escitalopram in P-glycoprotein deficient mice after acute and chronic treatment

Karlsson¹,

Carlsson²,

Hiemke³

et al. 2013

European Neuropsychopharmacology

View full text Add to dashboard Cite

According to both in vitro and in vivo data P-glycoprotein (P-gp) may restrict the uptake of several antidepressants into the brain, thus contributing to the poor success rate of current antidepressant therapies. The therapeutic activity of citalopram resides in the S-enantiomer, whereas the R-enantiomer is practically devoid of serotonin reuptake potency. To date, no in vivo data are available that address whether the enantiomers of citalopram and its metabolites are substrates of P-gp. P-gp knockout (abcb1ab (-/-)) and wild-type (abcb1ab (+/+)) mice underwent acute (single-dose) and chronic (two daily doses for 10 days) treatment with citalopram (10 mg/kg) or escitalopram (5 mg/kg). Serum and brain samples were collected 1-6 h after the first or last i.p. injection for subsequent drug analysis by an enantioselective HPLC method. In brain, 3-fold higher concentrations of S-and R-citalopram, and its metabolites, were found in abcb1ab (-/-) mice than in abcb1ab (+/+) mice after both acute and chronic citalopram treatments. After escitalopram treatment, the S-citalopram brain concentration was 3-5 times higher in the knockout mice than in controls. The results provide novel evidence that the enantiomers of citalopram are substrates of P-gp. Possible clinical and toxicological implications of this finding need to be further elucidated.

show abstract

“…Several methods have been devised for the determination of citalopram in pharmaceutical preparations and biological fluids. These include high performance liquid chromatography (HPLC) with UV detectors (Olesen and Linnet, 1996;Duverneuil et al, 2003;Frahnert et al, 2003), HPLC with fluorescence detectors (Matsui et al, 1995;Rochat et al, 1995;Meng and Gauthier, 2005), HLPC/mass spectrometry (Juan et al, 2005; . Gutteck and Rensch, 2003;Kollroser and Schober, 2003), gas chromatography (Gergov et al, 2000;Sane et al, 2002), electrophoretic methods (Flores et al, 2004;Buzinkaiova and Polonsky, 2000;Bjorhovde et al, 2003) and spectrophotometric (Asad, 2006;Asad et al, 2008;Badiadka and Kunnummel, 2010) methods.…”

Section: Introductionmentioning

confidence: 99%

Application of Methyl Orange in the Spectrophotometric Determination of Citalopram and Dapotextine in Pharmaceutical Formulations

El‐Didamony¹,

Abo-Elsoad²

2016

J App Pharm Sci

View full text Add to dashboard Cite

A simple, rapid and sensitive spectrophotometric method has been proposed for the assay of citalopram (CIT) and dapotextine (DPT) in bulk and pharmaceutical formulations. The method based on the reaction of the selected drugs with methyl orange (MO) in buffered aqueous solution at pH = 5.0 and pH = 3.0 for CIT and DPT, respectively. The formed yellow ion-pair complexes were extracted with dichloromethane and their absorbance was measured at 422 nm. The best conditions of the reaction were studied and optimized. The extracts are intensely colored and very stable at room temperature. The calibration graphs were linear over the concentration range of 1.2 -4.8 g/ml for CIT and 0.4 -4.0 g/ml for DPT. The drug-dye stoichiometric ratio as determined by the Job's method was found to be 1:1. The proposed method was successfully applied for determination of the drugs in tablets with good accuracy and precision. Excipients used as additive in commercial formulations did not interfere in the analysis. The proposed method can be recommended for quality control and routine analysis where time, cost effectiveness and high specificity of analytical technique are of great importance.

show abstract

Analysis of Enantiomers of Citalopram and Its Demethylated Metabolites in Plasma of Depressive Patients Using Chiral Reverse-Phase Liquid Chromatography

Cited by 114 publications

References 0 publications

In vivo steady‐state pharmacokinetic outcome following clinical and toxic doses of racemic citalopram to rats

In vivo steady‐state pharmacokinetic outcome following clinical and toxic doses of racemic citalopram to rats

Altered brain concentrations of citalopram and escitalopram in P-glycoprotein deficient mice after acute and chronic treatment

Application of Methyl Orange in the Spectrophotometric Determination of Citalopram and Dapotextine in Pharmaceutical Formulations

Contact Info

Product

Resources

About