Nanogram/mL detection of nortriptyline: Preparation of a molecularly imprinted polymer for spectrophotometric determination of nortriptyline based on multivariate optimization methods

In this work, the molecularly imprinted polymer was used as a selective sorbent in solid‐phase extraction method for the spectrophotometric determination of nortriptyline at 239 nm. Molecularly imprinted polymer was synthesized by pyrrole as a functional monomer in the presence of nortriptyline as a template. Several factors, consist of the concentration of the monomer to template ratio, amount of initiator, stirring rate, reaction time, the pH of the buffer solution, amount of sorbent, loading time, shaking rate of loading, extraction time, and shaking rate of extraction were evaluated due to their effectiveness in the preparation and extraction capability of molecularly imprinted polymer. Multivariate optimization methods, such as Plackett‐Burman and central composite designs, were employed to find and optimize the significant factors. Under the selected optimal conditions, molecularly imprinted polymer showed a linear range from 0.1 to 100 µmol/L (0.026 to 26 µg/mL) nortriptyline, a detection limit of 10.3 nmol/L (2.7 ng/mL), a highly repeatable (relative standard deviation of 3.7%) and reproducible response (relative standard deviation of 4.6%), and a good selectivity in the presence of structurally related molecules. Furthermore, molecularly imprinted polymer showed high extraction efficiency and was successfully used for the determination of nortriptyline in real samples.     

Development and validation of a highly sensitive LC‐MS/MS method for simultaneous quantitation of nortriptyline and 10‐hydroxynortriptyline in human plasma: application to a human pharmacokinetic study

A highly sensitive and specific LC‐MS/MS method has been developed for simultaneous estimation of nortriptyline (NTP) and 10‐hydroxynortriptyline (OH‐NTP) in human plasma (250 µL) using carbamazepine as an internal standard (IS). LC‐MS/MS was operated under the multiple reaction‐monitoring mode using the electrospray ionization technique. A simple liquid–liquid extraction process was used to extract NTP, OH‐NTP and IS from human plasma. The total run time was 2.5 min and the elution of NTP, OH‐NTP and IS occurred at 1.44, 1.28 and 1.39 min, respectively; this was achieved with a mobile phase consisting of 20 mm ammonium acetate : acetonitrile (20:80, v/v) at a flow rate of 0.50 mL/min on a HyPURITY C₁₈ column. The developed method was validated in human plasma with a lower limit of quantitation of 1.09 ng/mL for both NTP and OH‐NTP. A linear response function was established for the range of concentrations 1.09–30.0 ng/mL (r > 0.998) for both NTP and OH‐NTP. The intra‐ and inter‐day precision values for NTP and OH‐NTP met the acceptance as per FDA guidelines. NTP and OH‐NTP were stable in a battery of stability studies, i.e. bench‐top, auto‐sampler and freeze–thaw cycles. The developed assay was applied to a pharmacokinetic study in humans. Copyright © 2010 John Wiley & Sons, Ltd.     

Development and validation of amitriptyline and its metabolite in human plasma by ultra performance liquid chromatography-tandem mass spectrometry and its application to a bioequivalence study

A method based on ultra performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) in combination with solid‐phase extraction for sample pretreatment has been developed for the simultaneous analysis of amitriptyline and its main metabolite in human plasma. The extraction of the analytes from plasma samples was carried out by means of a selective SPE procedure using hydrophilic–lipophilic balance cartridges. The assay involves a simple solid‐phase extraction (SPE) procedure of 0.2 mL of human plasma and analysis was performed on a triple‐quadrupole tandem mass spectrometer by multiple reactions monitoring (MRM) mode via electrospray ionization (ESI). The standard calibration curve was linear over the ranges 0.370–95.539 ng/mL for amitriptyline and 0.365–94.374 ng/mL for nortriptyline, expressed by the linear correlation coefficient r², which was better than 0.995 for both. The intra‐ and inter‐day precision and accuracy of the quality control samples were within 10.0%. The recovery was 85.3, 88.4 and 80.7% for amitriptyline, nortriptyline and doxepin respectively. Total run time was 1.2 min only for each sample, which makes it possible to analyze more than 400 samples per day. The method was highly reproducible and gave peaks with excellent chromatography properties. Copyright © 2010 John Wiley & Sons, Ltd.     

Application of ionic liquid-based ultrasonic-assisted microextraction coupled with HPLC for determination of citalopram and nortriptyline in human plasma

In this paper, an effective and environmentally friendly method of ultrasound-assisted ionic liquid-based dispersive liquid–liquid microextraction (UA-IL-DLLME) combined with high-performance liquid chromatography (HPLC)–photodiode array detector was applied for extraction and determination of two antidepressant drugs citalopram hydrobromide and nortriptyline hydrochloride from human plasma samples. Several important parameters affect the steps and efficiency of extraction, some of which are sample solution’s pH, type and volume of ionic liquid, ultrasonic time, centrifuging time and rate, and the ionic strength of solution. Optimum conditions were obtained at pH?=?11, 1-octyl-3-methyl imidazolium hexafluorophosphate for ionic liquid, 55?µL for ionic liquid volume, 4?min for ultrasonic time, 5?min and 3,500?rpm for centrifuging time and rotation’s speed, due to ionic strength by the addition of NaCl 1%. Under optimized conditions, the linearity was obtained in the range of 0.02–2,000?µg/L, with correlation coefficients higher than 0.995. The limits of detection were 10?µg/L for citalopram and 6?µg/L for nortriptyline. Preconcentration factors were 920 for citalopram and 800 for nortriptyline. The present method of UA-IL-DLLME combined with HPLC was successfully used for the determination of citalopram and nortriptyline drugs in real samples of human plasma.     

Synthesis of cobaltocenium salts for use as redox labels and their incorporation into Nafion films

A cobaltocenium label was covalently attached to two antidepressants, nortriptyline and desipramine, via an amide linkage, and also to the hydrazine derivative of the biologically important compound biotin (vitamin H), again via an amide linkage. Analytically pure samples of these new cobaltocenium salts could be obtained by chromatography on silica gel followed by elution with aqueous acetone solutions containing sodium chloride (NaCl). These positively charged cobaltocenium ions preconcentrate in a polyanionic Nafion film coated on a glassy carbon surface, albeit at different concentration levels. One factor which seems to influence the amount of cobaltocenium ion that enters the film is polarity since the cobaltocenium ion containing the rather polar biotin preconcentrates at the lowest level in the relatively hydrophobic Nafion. Square-wave voltammograms of Nafion films containing these cobaltocenium cations exhibit a one-electron, reversible, reduction wave at approximately ?1.1 V (vs Ag/AgCl) with peak currents that are sufficiently large to permit detection of 10^?8 M quantities of these substances in the bulk solution.     

Surface,micellar, and thermodynamic properties of antidepressant drug nortriptyline hydrochloride with TX‐114 in aqueous/urea solutions

This paper deals with a comprehensive study of the mixed micellization and adsorption behavior of mixed systems enclosing an amphiphilic antidepressant drug nortriptyline hydrochloride (NOT) and Triton X‐114 (TX‐114) (nonionic surfactant) in aqueous/urea (500 mmol·kg^?1 and 1000 mmol·kg^?1) solutions by tensiometric method. The NOT is used for the cure of depression. For comparison purpose cmc value of pure drug NOT was also evaluated by conductimetric technique. Different theoretical models like Clint, Rubingh, and Rosen were used to get information about the nature of interaction between the components in bulk and at the interface. Because of the occurrence of urea increase in the surface charge of the micelles was obtained resulting a delay of the micelles formation. The cmc values of the mixed systems of NOT and TX‐114 were found to be in between the cmc values of pure components, which signify nonideal mixed system having attractive interactions in the absence and presence of urea. Various parameters such as micellar mole fractions of TX‐114 (X₁^m, X₁^σ) in solution and at interface, interaction parameter (β^m/β^σ) in solution and at interface, and activity coefficient in solution and at interface were evaluated and discussed using Rubingh's and Rosen's models. Surface excess (Γ_max) increases that means minimum area per head group (A_min) decreases as mole fraction (α₁) of TX‐114 increases in the absence/presence of urea. Different thermodynamic parameters have been calculated and discussed. The ?G⁰_m values achieved are all negative both in the absence and occurrence of urea.     

Quantitative Determination of Nortriptyline And Desmethylnortriptyline In Human Plasma By Combined Gas Ciiromatography - Mass Spectrometry

Abstract

A quantitative method has been developed for the determination of the tricyclic antidepressant drug nortriptyline in plasma, utilizing a combined technique of gas chromatography - mass spectrometry called mass fragmentography. A metabolite, desmethylnortriptyline, may be analyzed in the same run. The compounds are first converted to their heptafluorobutyranide derivatives. A complete chromatogram takes less than five minutes. Quantitive determinations under the present conditions are possible down to a few nanograms of nortriptyline per milliliter. There is a good correlation between the new method and that previously used which was based upon in vitro ³ 11-acetylation labelling.     

Directly Suspended Droplet Microextraction and Analysis of Amitriptyline and Nortriptyline by GC

Directly Suspended Droplet Microextraction (DSDME) was used for the determination of two tricyclic antidepressant drugs (TCAs), amitriptyline and nortriptyline. In this technique, an aqueous sample is agitated with a stirring bar, creating a mild vortex at the center of the vial. A droplet of an immiscible organic solvent is placed at the bottom of the vortex. After 20 min a portion of the organic droplet is withdrawn with a syringe and injected into the GC. Experimental conditions, such as the extraction solvent, extraction time, solvent volume, stirring rate, pH and salt addition were optimized. In order to evaluate the practical application of the method, relative standard deviations, linearity range and limits of detection were calculated. Typical enrichment factors were 167 and 179 for amitriptyline and nortriptyline, respectively. The method was applied to the determination of these drugs in urine samples.