• Development and validation of a high-performance liquid chromatographic assay using solid-phase extraction for the novel antitumor agent pancratistatin in human plasma.

      Khan, Parveen; Abbas, Sayara; Petit, B; Caffrey, Robert; Megram, Victoria; McGown, Alan T; Paterson Institute for Cancer Research, Section of Drug Development and Imaging, Withington, Manchester, UK. pkhan@picr.man.ac.uk (1999-04-16)
      The stability of the experimental anti-tumour agent pancratistatin in human plasma has been investigated. A solid-phase extraction technique and an HPLC assay with external standards have been developed and validated. Extraction was performed using C18 cartridges and HPLC, analysis was performed on a 15 cm Hypersil BDS column using isocratic elution with 13% acetonitrile and aqueous solution of 1% (w/v) acetic acid. The lower limit of quantification for pancratistatin in 5% DMF-95% water was found to be 0.58 ng/ml (+/-10.58%) and 2.3 ng/ml (+/-9.2%) following extraction from human plasma. Mean recovery of 89.4% (+/-4.73%) was obtained over the concentration range 0.0023-9.45 microg/ml for a five day validation study. Pancratistatin was stable at room temperature in light or dark for at least 15 days, in the refrigerator at 4 degrees C for at least 16 days and in the freezer at -20 degrees C or -80 degrees C for at least 28 days. Under all conditions monitored, % recovery of pancratistatin from human plasma was greater than 95% and no evidence of degradation had occurred. There also was no loss of pancratistatin after three cycles of freezing and thawing.
    • Dimethanesulphonate esters in receptor mapping studies. 2. Antitumour activities of alkyl and alkoxy dimethanesulphonates substituted on a benzene nucleus.

      Hadfield, John A; Fox, Brian W; Caffrey, Robert; Department of Experimental Chemotherapy, Paterson Institute for Cancer Research, Christie Hospital Trust, Withington, Manchester, UK. (1992-06)
      The antitumour activities of 15 novel aromatic dimethanesulphonate esters were studied. Several alkyl and alkoxy compounds have shown good antitumour activity whilst similar isomers have proved ineffective as antitumour agents. These differences in activity have been correlated with the length of the sidechain substituents and their relative flexibilities.