Urine nicotine metabolite concentrations in relation to plasma cotinine during low-level nicotine exposure

Abstract

Introduction: Plasma or saliva cotinine concentrations are used widely as biomarkers of secondhand smoke (SHS) exposure and have been associated with the risk of SHS-related disease. Concentrations of cotinine and other nicotine metabolites are considerably higher in urine than in plasma or saliva, making chemical analysis easier. In addition, urine is often more convenient to collect in some SHS exposure studies. The optimal use of nicotine metabolites in urine, singly or in combination, with or without correction for urine creatinine concentration, to estimate plasma cotinine concentration with low-level nicotine exposure has not been determined.

Methods: We dosed 36 nonsmokers with 100, 200, or 400 microg deuterium-labeled nicotine (simulating exposure to SHS) by mouth daily for 5 days and then measured plasma and urine cotinine and metabolites at various intervals over 24 hr.

Results: A plasma cotinine concentration of 1 ng/ml corresponds on average to a daily intake of 100 microg nicotine. Cotinine concentrations in urine averaged four to five times those in plasma. Correction of urine cotinine for creatinine concentration improved the correlation between urine and plasma cotinine. Measuring multiple cotinine metabolites in urine did not improve the correlation with plasma cotinine, compared with the use of urine cotinine alone.

Discussion: Measurement of urine cotinine corrected for creatinine concentration appears to be the best predictor of plasma cotinine.

Figure 1.

Mean plasma cotinine concentrations at various times of day with three different levels of nicotine intake. Triangles = 400 μg/day (n = 12); squares = 200 μg/day (n = 12); diamonds = 100 μg/day (n = 12). Bars indicate SEM.

Figure 2.

Mean urine concentrations of cotinine, cotinine glucuronide, trans-3′-hydroxycotinine (3HC), and 3HC glucuronide at various times of day in subjects receiving 200 μg nicotine per day (n = 12). SEM for the analytes are not shown for the sake of clarity, but average SEMs throughout the day were 8.5 for cotinine-d2, 11.4 for cotinine-d2 glucuronide, 36.8 for 3HC-d2, and 15.1 for 3HC-d2 glucuronide. Factors to convert units from pmol/ml to ng/ml are 0.178, 0.354, 0.194, and 0.370 for the four analytes, respectively. MN = midnight.

Figure 3.

Plasma versus urinary cotinine concentrations using a 12-hr average plasma cotinine level and noon–4 p.m. urine cotinine concentrations. Data were from 36 subjects: 12 received 100 μg nicotine per day (diamonds), 12 received 200 μg/day (squares), and 12 received 400 μg/day (triangles). (A) Urine cotinine concentration corrected for creatinine concentration. (B) Uncorrected urine cotinine concentration.