Highly Sensitive Lc-MS/MS Method for the Determination of Clozapine in Rat Plasma: Application to a Preclinical Pharmacokinetic Study

Haas, Sandra Elisa; Brum, Larissa Picada; Andrade, Cristiane de; Azeredo, Francine Johansson; Pigatto, Maiara Cássia; Torres, Bruna Gaelzer Silva; Guterres, Sílvia Stanisçuaski; Costa, Teresa Dalla

doi:10.1080/10826076.2011.639118

Cited by 9 publications

(2 citation statements)

References 12 publications

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“…Moreover, a sample pretreatment procedure also seems like a crucial step for analytical method development. Techniques such as protein precipitation, liquid–liquid extraction (LLE), solid phase extraction (SPE), solid phase microextraction (SPME) and hollow fiber-based liquid phase microextraction (HF-LPME) have been used to extract and/or pre-concentrate drugs in the biological fluid before analytical system analysis [ 9 , 12 , 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Bioanalytical LC-QTOF/MS Method for a N-phenylpiperazine Derivate (LQFM05): An Anxiolytic- and Antidepressant-like Prototype Drug Applied to Pharmacokinetic and Biodistribution Studies

et al. 2023

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The LQFM05 is a prototype drug designed for treatment of psychiatric disorders, such as schizophrenia, exhibiting anxiolytic- and antidepressant-like (12 or 24 µmol/kg) effects in classical behavioral tests. In order to evaluate its pharmacokinetic properties, a liquid chromatography method coupled to a quadrupole time of flight mass spectrometry system (LC-QTOF/MS) was developed and fully validated for LQFM05 analysis in rat plasma and tissue samples (brain, heart, liver, and kidneys). Liquid–liquid extraction, solid phase extraction and protein precipitation were assessed as clean-up procedures for biological samples and analyte enrichment. Plasma and tissue samples underwent protein precipitation as a preliminary step, using acetonitrile. Linearity was fully demonstrated for the dynamic range (10.0 to 900.0 ng/mL), with r2 values higher than 0.99 (RSDslope ≤ 2%, Fcal < Ftab, Ccal < Ctab). Biodistribution studies in rats revealed high brain tissue concentrations (12.4 µg/g), suggesting elevated drug affinity to the main therapeutic target tissue, showing a blood partition coefficient of 1.9. Kidneys also showed great exposure and tissue affinity, suggesting a potential extrahepatic clearance. Likewise, all examined tissues exhibited satisfactory LQFMF05 distribution. The mass fragmentation spectrum indicated the presence of its main metabolite, LQFM235, yielded by high hepatic hydroxylation route, an equally bioactive derivative. Lastly, the developed LC-QTOF/MS method was shown to be sensitive (LOQ = 10 ng/mL), precise and accurate for LQFM05 determination in tissue homogenates and plasma samples.

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Section: Introductionmentioning

confidence: 99%

Bioanalytical LC-QTOF/MS Method for a N-phenylpiperazine Derivate (LQFM05): An Anxiolytic- and Antidepressant-like Prototype Drug Applied to Pharmacokinetic and Biodistribution Studies

et al. 2023

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“…Various techniques for clozapine assessment were reported. Liquid chromatography [ 19 , 20 , 21 , 22 ], HPLC [ 23 , 24 , 25 , 26 ], GC [ 27 ], electrophoresis [ 28 , 29 ], voltammetry [ 30 , 31 , 32 ], and spectrophotometric [ 33 , 34 , 35 ] are among these approaches. The majority of these solutions have some downsides.…”

Section: Introductionmentioning

confidence: 99%

Selective Spectrofluorimetric Approach for the Assessment of Two Antipsychotic Drugs through Derivatization with O-Phthalaldehyde

et al. 2022

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A facile and sensible spectrofluorimetric approach for the measurement of two antipsychotic medications, aripiperazole (ARP) and clozapine (CLZ), was devised and validated. The approach involves reacting the examined medicines with o-phthalaldehyde in the presence of β-mercaptoethanol in a borate buffer of pH 9.0 and pH 10 for ARP and CLZ, respectively, to produce a robustly fluorescent compound that is detected at 450 nm following excitation at 340 nm. The experimental variables influencing the performance and product stability were thoroughly investigated and optimized. Under optimal conditions, the intensity of the fluorescence was linear during a concentration range of 0.1–0.5 μg/mL, with a limit of detection (0.0391 and 0.0400 μg/mL) and limit of quantitation (0.1035 and 0.1332 μg/mL), respectively, for ARP and CLZ. The suggested approach was successful in analyzing commercialized tablets. A statistical investigation of the results produced by the suggested and standard methods showed no remarkable variation in the precision and accuracy of the two approaches. A chemical mechanism using o-phthalaldehyde was proposed.

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Clozapine-loaded nanocapsules improve antipsychotic activity in rats: building a sequential PopPK/PD model to discriminate nanocarriers in the preformulation step

Funguetto-Ribeiro,

Maciel,

Lunardi

et al. 2023

Pharm Res

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Highly Sensitive Lc-MS/MS Method for the Determination of Clozapine in Rat Plasma: Application to a Preclinical Pharmacokinetic Study

Cited by 9 publications

References 12 publications

Bioanalytical LC-QTOF/MS Method for a N-phenylpiperazine Derivate (LQFM05): An Anxiolytic- and Antidepressant-like Prototype Drug Applied to Pharmacokinetic and Biodistribution Studies

Bioanalytical LC-QTOF/MS Method for a N-phenylpiperazine Derivate (LQFM05): An Anxiolytic- and Antidepressant-like Prototype Drug Applied to Pharmacokinetic and Biodistribution Studies

Selective Spectrofluorimetric Approach for the Assessment of Two Antipsychotic Drugs through Derivatization with O-Phthalaldehyde

Clozapine-loaded nanocapsules improve antipsychotic activity in rats: building a sequential PopPK/PD model to discriminate nanocarriers in the preformulation step

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