Atomoxetine hydrochloride

Molecular formula C17H21NO.HCI Molecular weight 291.82 CAS Registry No 82248-59-7 

Sample preparation Add 500 [iL plasma to a Varian SDB-XC SPE cartridge, wash with 1 mL MeOHiwater 15 85, elute with 750 p.L MeCN containing 0.1% trifluoroacetic acid. Evaporate the eluate to dr5uiess under a stream of nitrogen at 45°, reconstitute the residue with 100 gL MeCN, mix with 25 p.L water, inject an aliquot. 

Mobile phase MeCNiwater 85 15 containing 5 mM ammonium acetate, 0.2% formic acid, and 0.03% trifluoroacetic acid 

Detector MS, PE Sciex API III, MS/MS, positive atmospheric pressure chemical ionization, heated nebulizer interface, m/z 256 to 44 

Sample preparation Plasma. Mix 3 mL MeCN with 1.5 mL plasma, centrifuge, evaporate the supernatant to dryness under a stream of nitrogen, reconstitute the residue with 200 rL MeCN water 10 90, inject an aliquot. Urine. Lyophilize urine, reconstitute with MeCN water 10 90 to one-tenth original volume, vortex. Alter (0.45 xm), inject an aliquot. 

---

Sauer JM, Long AJ, Ring B, et al Atomoxetine hydrochloride clinical drug-drug interaction prediction and outcome. J Pharmacol Exp Ther 308 410- 18,2004... 

Gavin, P.R and Olsen, B.A. A quality by design approach to impurity method development for atomoxetine hydrochloride (LY139603). J. Pharm. Biomed. 2008, 46, 431 1. 

Caballerro J, Nahata MC. Atomoxetine hydrochloride for the treatment of ADHD. Chn Ther 2003 25 3065-3083. 

Sauer JM, Ponsler GD, Mattiuz EL, et al. Disposition and metabolic fate of atomoxetine hydrochloride the role of CYP2D6 in human disposition and metabolism. Drug Metab Dispos 2003 31 98-107. 

Strattera (Atomoxetine hydrochloride). Eli Lilly and Company. US prescribing information. May 2007. 

Johnson M, Cederlund M, Rdstam M, Areskoug B, Gillberg C. Open-label trial of atomoxetine hydrochloride in adults with ADHD. J Atten Disord 2010 13(5) 539 5. 

Adderall XR (package insert). Wayne, PA, Shire US Inc, 2004 Angrist B, d Hollosy M, Sanfilipo M, et al Central nervous system stimulants as symptomatic treatments for AIDS-related neuropsychiatric impairment. J Clin Psychophamiacol 12 268—272, 1992 Arnold LE, Lindsay RL, Connors CK, et al A douhle-hlind, placebo-controlled withdrawal trial of dexmethylphenidate hydrochloride in children with attention-deficit hyperactivity disorder. I Am Acad Child Adolesc Psychiatry 14 542—554, 2004 Belle DJ, Ernest CS, Sauer JM, et al Effect of potent CYP2D6 inhibition by paroxetine on atomoxetine pharmacokinetics. I Clin Pharmacol 42 1219-1227, 2002... 

Minor stmctural modifications to the fluoxetine stmcture may have an impact on selectivity. For example, removal of the trifiuoromethyl group on the para position of the phenoxy ring and attachment of a methoxy group to the ortho position resulted in the discovery of nisoxetine, an effective blocker of the noradrenaline reuptake transport protein NAT (Fig. 18.26). Replacement of the methoxy with a methyl group appears to be tolerated by NAT, which leads to atomoxetine, a selective NAT inhibitor. This derivative has non-stimulant properties and is used in the treatment of ADHD in adults and children. It is available as the hydrochloride salt and dosages can range between 40 and 100 mg. The formulated product only contains the (R)-enantiomer. 

---