Effect of sample collection tubing type used in a clinical study on quantitation of pharmaceutical compounds in CSF by LC–MS/MS

Background: Plasma/cerebrospinal fluid (CSF) ratio of compound K was determined to be lower than predicted during the conduct of clinical study. This triggered the evaluation of nonspecific binding of drug K and an additional ten compounds in CSF to collection tubing. Physiochemical properties such as pKa and log D values were correlated to the quantified results. Results: Mean recoveries of compound K quality controls sampled within 24 h, as compared with spiked quality control, were 12.9, 44.4 and 77.7% from silicone, Tygon® and Pharmed® collection tubing, respectively. Eight out of ten compounds showed significant loss into silicone and seven out of ten compounds showed no significant loss into Pharmed. Conclusion: Silicone tubing is not recommended and Pharmed appears to be most appropriate. CSF sample collection tubing must be evaluated prior to starting clinical studies.