, 1991) data were collected. 3-HC/Cotinine and Nicotine Levels Saliva samples collected during eligibility assessment were examined to determine 3-HC/cotinine using liquid chromatography CP-868596 with tandem mass spectrometry (Dempsey et al., 2004). The 3-HC/cotinine ratio has been shown to be independent from time since last cigarette and stable over repeated measures (Lea et al., 2006; Mooney et al., 2008). While plasma was used previously to ascertain the rate of nicotine metabolism, the reliability and validity of using saliva samples for 3-HC/cotinine has also been demonstrated (Dempsey et al., 2004) and was selected for this study given its ease of collection, storage, and shipping. A 3-HC/cotinine value of �� .

18 was used, a priori, to select participants with 3-HC/cotinine values that were within the top three quartiles of the 3-HC/cotinine saliva distribution (Dempsey et al., 2004). It is worth noting that this value is lower than the value used to identify the top three quartiles of the 3-HC/cotinine distribution when plasma is used (i.e., 0.23�C0.26; Lerman et al., 2006; Schnoll et al., 2009). Nicotine and cotinine levels in saliva at baseline and Week 1 were also determined using liquid chromatography with tandem mass spectrometry (Dempsey et al., 2004) in order to determine nicotine and cotinine percent replacement, versus baseline levels. To ensure that the Week 1 measures of nicotine and cotinine levels were not confounded by smoking, Week 1 saliva samples were collected only among participants who were confirmed abstinent using CO breath samples (�� 10 ppm).

Patch Adherence Patch adherence was measured by self-report. At each assessment from Week 0�C8, participants indicated if they used the patches on each day. Participants were classified as compliant for a week if they used patches on 6 days or more each week (Schnoll et al., 2010). Side Effects Side effects were assessed using a symptom checklist from past trials (Schnoll et al., 2010). The checklist was administered at Weeks ?1, 0, 1, 3, 5, and 8. Each symptom (e.g., nausea, skin reaction) was rated from 1 (none) to 4 (severe). Participants were instructed to contact study personnel if they experienced any serious medical problems between assessments. Adverse events were considered serious if the participant considered them debilitating or if they required hospitalization.

Batimastat Serious adverse events were reported to the University of Pennsylvania IRB and were classified as related or unrelated to treatment arm allocation. At Weeks 1 and 8, an ECG was administered and blood pressure was assessed. Smoking Cessation At Week 1 and Week 8 (end of treatment), participant quit rates were assessed. A time-line follow-back measure was used to assess daily smoking from Week 0 to Week 8. A breath sample was collected at Week 1 and Week 8 to verify self-reported abstinence using a CO monitor. Two primary outcome measures were used for this study.