Nortriptyline, separation

Note Derivatization with this reagent sequence in combination with extraction and TLC separation is speciftc for amitriptyline and nortriptyline in the analysis of plasma furthermore its high sensitivity allows its employment in pharmacokinetic studies, e. g. after the oral administration of a single dose of 25 mg amitriptyline. 

Fi re 4.15 Separation of the tricyclic antidepressant amitriptyline and its major metabolites on a 10 cm x 4.6 mm I. D. column packed with Spherisorb S5H silica with methanol-aqueous ammonium acetate (9 1), pH 9.1, as mobile phase at a flow rate of about 1 ml/min. Peak identification 1 > amitriptyline-N-oxide 2 amitriptyline 3 - E-lO-hydroxyamitriptyline 4 - Z-10-hyroxyamitriptyline 5 desmethylnortrlptyline 6 nortriptyline 7 E-lO-hydroxynortriptyline and 8 - Z-lO-hydroxynortriptyline. (Reproduced with permission from ref. 271. Copyright Elsevier Scientific Publishing Co.)... 

FIGURE 6.16 Separation of 1 = phenol 2 = 2-naphthalene sulfonic acid 3 = p-xylenesulfonic acid 4 = caffeine 5 = nortriptyline 6 = diphenhydramine 7 = benzylamine 8 = procainamide on Atlantis silica column (25 x 0.46 cm, 5 xm particles). Mobile phase acetonitrile-0.1 M ammonium formate pH 3.0 (85 15, v/v), 1 mLmin b... 

FIGURE 2.4 Separation of strong bases on a classical RP and on a shielded phase. Columns Prontosil CIS H Prontosil CIS ace EPS (150x4.0mm). Mobile phase MeOH/phosphate buffer 20mM pH=7, 65/35 v/v, 40°C. Analytes 1, uracil 2, protriptyline 3, nortriptyline 4, doxepine 5, imipramine 6, amitriptyline 7, trimipramine S, clomipramine. 

Figure 1.29. LC separation of (1) norephedrine, (2) nortriptyline, (3) toluene, (4) imipnamine, and (5) amitriptyline using columns with various bonded phases [all-ACE column 250mmx4.6mm, 5 pm mobile phase 80/20 (v/v) methanol-25 mM phosphate buffer usually, phosphate buffers are not preferred for MS applications], (Reprinted with permission from Dolan, 2007.)...

Berger and Wilson also reported the separation of 10 antidepressants (amitriptyline, imipramine, nortriptyline, desipramine, protripyline, bucliz-ine, benactyzine, hydroxyzine, perphenazine, and thioridazine) using a packed-column SFC with a tertiary mobile phase [37], A Lichrosphere cyanopropyl column with a mobile phase consisting of supercritical fluid carbon dioxide with 10% modifier (methanol with 0.5% isopropylamine) was used for the separation. It was noted that solutes did not elute without the addition of isopropylamine. Detection limits obtained were as low as 88 ppb for a 5-jul injection. 

In recent work within our laboratories, we have evaluated a number of unbonded silicas by CEC specifically for the separation of a range of pharmaceutically relevant basic analytes and mixtures. We purposefully chose strong basic analytes that comprised a wide range of lipophilicities, molecular weights and log P values to robustly test the separation systems. The basic analyte test mixture contained two AstraZeneca R D compounds, benzylamine, nortriptyline, diphenhydramine and procainamide. 

Fig. 3.2. CEC separation of the basic test mixture using (A) Hypersil silica, (B) Hypersil BDS silica and (C) HyPURITY silica capillaries (100 pm i.d., 25 cm effective length, 33.5 cm total). Conditions 6 2 2 v/v/v ACN-H2O-5O mM TRIS, pH 7.8, 20 kV, 20°C, 5 kV/3 s injections, 210 nm. Injection mixtures in (A) and (C) were equivolume compositions of each base at 1 mg/ml and in (B), equivolume compositions of each base at 0.1 mg/ml. The EOF marked by biphenyl under these conditions and was similar on all phases at approximately 4 minutes. Peak identities I = AZ compound A, II = Benzylamine, III = Nortriptyline, IV = Diphenhydramine, V = AZ compound B and VI = Procainamide. Adaptation of [20]. Reproduced with the permission of Chromatographia.

Spherisorb propyl SCX (3 pm) Spherisorb phenyl SCX (3 pm) Symmetry SCX (3 pm) Spherisrob Mixed Mode (3 pm) Evaluation of various SCX phases, compariosn of electroosomotic mobility at various pHs, separation of antidepressants, amitriptyline, nortriptyline, neutral test mixture MeCN-50 mM phosphate 70 30, pH 2.3 MeCN-20 mM borate 70 30, pH 9.0 [97]... 

Figure 5-7. (a) Structures of cis and trans isomers of Doxepin and (b) normal-phase chromatographic separation of isomers of doxepin. I, c -doxepin II, frans-doxepin III, nortriptyline IV, cw-V-desmethyldoxepin V, fram-V-desmethyldoxepin. Chromatographic conditions Column Spherisob silica, 150 x 4.5mm, 3pm. Hexane methanol nonylamine, 95 5 0.3 (v/v/v) flow rate, l.OmL/min detection, 254nm temperature, 23°C. (Reprinted from reference 41, with permission.)... 

Figure 18-5. The separation of therapeutic tricyclic antidepressants on PBD-coated zirconia at different temperatures. Solutes 1, lidnocaine 2, quinidine 3, norephedrine 4, tryptamine 5, amitriptyline 6, nortriptyline. (Reproduced from reference 52, with permission. Copyright 1997, American Chemical Society.)...

Piperaki, S. Parissi-Poulou, M. Koupparis, M. A separation study of tricyclic antidepressant drugs by HPLC with p-cyclodextrin bonded stationary phase. J.Liq.Chromatogr, 1993, 16, 3487-3508 [simultaneous chloripramine, doxepin, imipramine, maprotiline, nortriptyline, protriptyline]... 

Tricyclic antidepressants were analyzed by Vallano et al. [179] via an MIP-CEC separation. In this separation, doxepin, imipramine, amitriptyline, trimipramine, and clomipramine were separated from the template molecule nortriptyline (Figure 5.22). The capillary inner diameter and total length were 100 pm and 33 cm, respectively, and the total length of the monolithic bed was 22.5 cm. The eluent was 92 2 ACN 10 mM sodium acetate pH 3.0 to which 0.02% trifluoracetic acid and 0.015% triethylamine (TEA) (v/v) was added. A constant applied voltage of 30 kV was utilized. 

You are required to separate amitriptyline and nortriptyline using HPLC (chemical structures shown here). 

Figure 6.7 Electropherogram of (in migration order) amphetamine, methamphetamine, pethidine, nortriptyline, methadone, haloperidol, and loperamide (lOjxgml of each) separated on a 63.5 cm x 75 im ID fused...

Po and Irwin (1979) used TLC to separate numerous tricyclic neuroleptic tranquilizers. Samples were dissolved in ethyl acetate, and the mobile phase consisted of mixtures of different n-alcohols with water. Circular development in a Camag U chamber was used, and spots were detected by fluorescence quenching. The /Jp values of some of the better known drugs developed in methanol-water (90 10) were amitriptyline, 0.17 clopenthixol, 0.40 doxepin, 0.42 nortriptyline, 0.37 and promazine, 0.14. Shirke et al. (1994) determined amitriptyline and chlordiazepoxide in combined dosage forms using ethyl acetate-methanol-dieth-ylamine (9.5 0.5 0.05) mobile phase and scanning at 245 nm. 

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