Cocaine and metabolite concentrations in DBS and venous blood after controlled intravenous cocaine administration

Abstract

Background: DBS are an increasingly common clinical matrix.

Methods & results: Sensitive and specific methods for DBS and venous blood cocaine and metabolite detection by LC-HRMS and 2D GC-MS, respectively, were validated to examine correlation between concentrations following controlled intravenous cocaine administration. Linear ranges from 1 to 200 µg/l were achieved, with acceptable bias and imprecision. Authentic matched specimens' (392 DBS, 97 venous blood) cocaine and benzoylecgonine concentrations were qualitatively similar, but DBS had much greater variability (21.4-105.9 %CV) and were lower than in blood.

Conclusion: DBS offer advantages for monitoring cocaine intake; however, differences between capillary and venous blood and DBS concentration variability must be addressed.

Figure 1.. Cocaine and benzoylecgonine in DBS and matched blood samples from participant L, 60 min after 25 mg intravenous cocaine.

(A) LC–MS/MS chromatogram of DBS specimen with 42.9 µg/l cocaine and 78.5 µg/l BE. Norcocaine was not detected. (B) Corresponding venous blood 2D GC–MS chromatogram with 40.7 µg/l cocaine and 107.4 µg/l BE. BE: Benzoylecgonine.

Figure 2.. Median cocaine and benzoylecgonine concentrations in DBS and venous blood from 13 participants 30, 60 and 90 min following 25 mg/kg intravenous cocaine administrations on three separate days (days 1, 5 and 10).

Error bars represent one standard deviation constrained to 0. BE: Benzoylecgonine.

Figure 3.. Comparison between venous blood and DBS cocaine and benzoylecgonine concentrations in simultaneously collected specimens from 13 participants 30, 60 and 90 min following 25 mg/kg intravenous cocaine administration on three separate days (days 1, 5 and 10).

Only paired venous blood-DBS specimens within the linear range were included in correlations and Bland-Altman analysis plots: cocaine (n = 87) and benzoylecgonine (BE) (n = 90). (A) Correlation of venous blood with median DBS cocaine and BE concentrations. Regression was calculated by least-squares regression analysis. (B) Bland-Altman analysis plots comparing blood and DBS collection methods for cocaine and BE detection. Dotted lines represent the 95% limits of agreement (mean difference ± 2SD).