Journal of Chromatography B, 854 (2007) 128–134 Determination of atomoxetine in human plasma by a high performance liquid chromatographic method with ultraviolet detection using liquid–liquid extraction Wei Guo, Wenbiao Li ∗ , Guixin Guo, Jun Zhang, Beilei Zhou, Yimin Zhai, Chuanyue Wang Laboratory of Clinical Psychopharmacology, Beijing Anding Hospital, Capital Medical University, AnKang Lane 5#, Deshengmen Wai, Xicheng District, Beijing 100088, China Received 7 December 2006; accepted 3 April 2007 Available online 13 April 2007 Abstract A HPLC method with UV detection (210nm) was developed and validated for the quantification of atomoxetine, a new medication for the treatment of attention deficit/hyperactivity disorder, in human plasma. Following a two-step liquid–liquid extraction with diethyl ether, the analyte and internal standard (maprotiline) were separated using an isocratic mobile phase of acetonitrile/phosphate buffer (39/61, v/v, pH 6.6) on a reverse phase Inertsil C 18 column. Linearity was verified over the range of 3.12–200 ng/mL atomoxetine in plasma. The lowest limit of detection is 2.5 ng/mL (S/N = 10). This HPLC method was validated with within- and between-batch precisions of 4.9–14.4% and 4.7–13.1%, respectively. The within- and between-batch biases were -1.9 to 1.4% and 0.1–13.8%, respectively. Commonly used psychotropic drugs and frequently coadministered drugs did not interfere with the drug and internal standard. This method is simple, economical and specific, and has been used successfully in a pharmacokinetic study of atomoxetine. © 2007 Elsevier B.V. All rights reserved. Keywords: Atomoxetine; Liquid–liquid extraction; HPLC; Pharmacokinetic 1. Introduction Atomoxetine, a new therapeutic drug chemically known as (-)-N-methyl-3-phenyl-3-(o-tolyloxy)-propylamine hydro- chloride (Fig. 1), was approved by the United States FDA in 2003 to treat attention deficit/hyperactivity disorder (ADHD) [1]. ADHD is a common neurobehavioral disorder marked by symptoms of inattention, hyperactivity and impulsiveness, which impair academic and social functioning. The disorder begins early in life, and the symptoms of some patients persist to adulthood. The prevalence of ADHD in children is 6–10% in the United States [2], 5–16% in Europe [3] and 3–13% in China [4,5]. Atomoxetine is the first approved non-stimulant drug for the treatment of ADHD. Prior to atomoxetine approval, most of children and adults diagnosed with ADHD were treated with psychostimulants such as methylphenidate, dexamfetamine, and ∗ Corresponding author. Tel.: +86 10 82085468; fax: +86 10 62064460. E-mail address: wenstonli@yahoo.com.cn (W. Li). pemoline, among others. Psychostimulants have been demon- strated to be effective in relieving the symptoms of ADHD [6,7]. These drugs exert their pharmacological effects via the mechanism of increasing availability of extracellular dopamine by blocking dopamine transporters and in some cases enhanc- ing dopamine release [8]. The main problems associated with these medications are their potential for abuse, and failure to respond in some patients. Atomoxetine is a potent inhibitor of the presynaptic norepinephrine transporter, with minimal affinity for other noradrenergic receptors or for other neurotransporters or receptors [9,10]. It is not a stimulant and does not have the abuse potential associated with psychostimulants [11]. Several pharmacokinetic studies of atomoxetine with sin- gle and multiple doses in healthy volunteers [12–15], children and adolescents with ADHD [16], and ADHD patients with hepatic impairments [12] have been reported. Of note, most reports were from western populations. A systematic review of the pharmacokinetics of atomoxetine was recently published by Sauer et al. [17]. However, the pharmacokinetics of atomoxe- tine in different ethnic groups, the influence of co-medication on the concentration of atomoxetine, therapeutic drug mon- 1570-0232/$ – see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.jchromb.2007.04.007