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.