Stereoselective determination of citalopram and desmethylcitalopram in human plasma and breast milk by liquid chromatography tandem mass spectrometry.
- Weisskopf E School of Pharmaceutical Sciences, University of Geneva and University of Lausanne, Geneva, Switzerland.
- Panchaud A School of Pharmaceutical Sciences, University of Geneva and University of Lausanne, Geneva, Switzerland; Division of Clinical Pharmacology, Lausanne University Hospital, Lausanne, Switzerland.
- Nguyen KA Department of Neonatology, Hospices Civils de Lyon, Lyon, France.
- Grosjean D EPICIME-CIC 1407, Inserm, Service of Clinical Pharmacology, CHU-Lyon, Bron, France.
- Hascoët JM Department of Neonatology, Maternité Régionale, Université de Lorraine, Nancy, France.
- Csajka C School of Pharmaceutical Sciences, University of Geneva and University of Lausanne, Geneva, Switzerland; Division of Clinical Pharmacology, Lausanne University Hospital, Lausanne, Switzerland.
- Eap CB School of Pharmaceutical Sciences, University of Geneva and University of Lausanne, Geneva, Switzerland; Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
- Ansermot N Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland. Electronic address: nicolas.ansermot@chuv.ch.
- 2016-09-09
Published in:
- Journal of pharmaceutical and biomedical analysis. - 2016
Breast milk
Citalopram
Enantiomer
LC–MS/MS
Plasma
Quantification
Chromatography, High Pressure Liquid
Chromatography, Reverse-Phase
Citalopram
Humans
Milk, Human
Reproducibility of Results
Solid Phase Extraction
Spectrometry, Mass, Electrospray Ionization
Stereoisomerism
Tandem Mass Spectrometry
English
A high performance liquid chromatography (HPLC) tandem mass spectrometry (MS/MS) method was developed for the simultaneous, stereoselective quantification of the antidepressant citalopram and its active metabolite desmethylcitalopram in human plasma and breast milk. Sample preparation was performed by a two-step approach, including generic protein precipitation with acetonitrile followed by solid phase extraction. Enantiospecific separation of analytes was achieved on a Phenomenex® Lux Cellulose-2 column (4.6mm×150mm; 5μm), using reversed phase chromatography conditions characterized by a gradient elution of ammonium acetate buffer (pH 9.0; 20mM) and acetonitrile at a flow rate of 0.6ml/min. The compounds were detected by a tandem quadrupole mass spectrometer equipped with an electrospray ionization source and operating in multiple reaction monitoring mode. The method was fully validated in both biological fluids over a large concentration range of 0.1-100ng/ml for S-(+)- and R-(-)-citalopram, and 0.3-100ng/ml for S-(+)- and R-(-)-desmethylcitalopram. Trueness (90.0-113.3% and 97.1-103.6%), repeatability (0.9-15.9% and 0.9-8.4%) and intermediate precision (1.3-17.8% and 0.9-9.6%) in plasma and breast milk, respectively, meet international guidelines for method validation. Internal standard-normalized matrix effects ranged between 99 and 101% and 98-105%, respectively. The accuracy profiles (total error of trueness and precision) were mostly within the acceptance limits for biological samples defined as ±30%. The method was successfully applied to patient samples in a clinical trial setting.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1016/j.jpba.2016.08.014
- PMID 27606925
- Persistent URL
- https://sonar.ch/global/documents/34044
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