Doxepin separation

Figure 15.3 Separation of tricyclic antidepressants by using multidimensional LC-LC. Peak identification is as follows DOX, doxepin DES, desipramine NOR, noitryptylene IMI, imipramine AMI, amiti yptyline. Adapted from Journal of Chromatography, 507, J. V. Posluszny et al., Optimization of multidimensional high-performance liquid cliromatography for the deterTnination of drugs in plasma by direct injection, micellar cleanup and photodiode array detection , pp. 267 - 276, copyright 1990, with permission from Elsevier Science.

C) Preparation of Doxepin 1,530 grams of the product from step (B) is suspended in 4.5 liters dry tetrahydrofuran and 6.0 mols of butyl lithium in heptane is added during 1 hour. After an additional 30 minutes, 483 grams of 6,1 I dihydrodibenz-lb.eloxepin-ll-one, prepared as described in Belgian Patent 641,49B, is added to the deep red solution and the reaction was maintained at reflux for 10 hours. Water, 500 ml, is added at room temperature and the solvent is removed in vacuo. The crude residue is treated with 10% hydrochloric acid until acidic (pH 2) and then 1.5 liters benzene is added. After stirring, the mixture separates into 3 phases (an insoluble hydrochloride salt product phase, an aqueous phase and an organic phase). 

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. 

Separations involving cis/trans isomers can also be accomplished by employing NPC. An example of this application is the separation of tricyclic antidepressant doxepin, which is marketed as a mixture of geometric isomers in a cis/trans ratio of 15 85 [41], When a spherisorb silica column is used with a hexane-methanol-nonylamine mobile-phase system, the cis isomer of doxepin elutes first. The structures of the two isomers and the chromatographic separation are shown in Figure 5-7. NPC has also been successfully employed in the separation of cis/trans isomers of steroids. Four diastereomers... 

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.)... 

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. 

Fig. 4 Effect of the separation buffer type on stacking at a sample loading of 12% of the capillary volume. Top Borate buffer 210 mM, pH 8.6 bottom triethanolamine 160 mM, tricine 50 mM, pH 8.6 containing 10% acetonitrile. Separation of a mixture of weakly cationic and weakly anionic compounds in the same run doxepin (D, 50 mg/L), A -acetylprocainamide (N, 50 mg/L), quinine (Q, 20 mg/L), theophylline (T, 50 mg/L) and iothalamic acid (I, 20 mg/L) at 14 kV, 254 nm (M = Electro-osmotic flow).

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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