Bioequivalence and Bioavailability Forum

Dear Raghavendra!

❝ Please clarify me the issues associated with sampling (plasma/serum or

❝ urine)? which one is best to quantify the drug, serum/plasma or urine?

Depends.
FDA (draft 2008) suggests urine. In the EU urine data are only acceptable in exceptional cases (due to analytical limitations). Even if you opt for a multiple dose study or SD in urine, EMA want's to see C_max in plasma. See the current guideline (Section "The use of urinary data"). Though MAs were granted in the past based on urinary data (Sweden 2008), plasma was used in more recent ones (UK 2009).

❝ In the published literature, the number of volunteers too largely vary

❝ from one article to another. How much sample size is required?

Not uncommon, especially for such a drug (clinical setting, sampling procedures & intervals, bioanalytical methods). I would opt for a pilot study.

❝ It seems only HPLC-Fluorescence detection technique is available for

❝ estimation of the drug. Is there any updates on analytical developments of

❝ this drug in serum?

In the UK-application LC/MS-MS was employed. Other methods may be used after adaption (see here for GC/MS of clodronate).