A method utilizing therm
al desorption m
ass spectrometry(TDMS) for the detection
and qu
antit
ation of free
acidforms in ph
arm
aceutic
al drug products formul
ated
ass
alts is presented. Selective detection of neutr
al drugforms is possible bec
ause the vol
atility of
a drug presentin its free
acid form is typic
ally much higher th
an th
at ofits corresponding s
alt forms, which h
ave negligible vol
atility even
at high temper
atures. T
andem m
ass spectrometric detection
allows selective qu
antit
ation of thedesired free
acid drug forms without signific
ant interferences from formul
ation excipients. The
applic
ation ofthe TDMS
appro
ach is demonstr
ated for
a sodium s
alt of
a represent
ative, c
arboxyl
ated drug molecule. Excellentsensitivity, specificity,
and
adequ
ate line
arity of detectorsign
al
as
a function of microgr
ams of free
acid
added weredemonstr
ated in the presence of the sodium s
alt of thedrug
and formul
ation excipients. The sensitivity of themethod w
as demonstr
ated
at free
acid levels of 0.6% w/w(6
![](/im<font color=)
ages/entities/mgr.gif">g
absolute m
ass). T
ablet s
amples were
an
alyzed bytherm
al desorption EI-MS/MS with reference to extern
alst
and
ards using
a commerci
ally
av
ail
able qu
adrupole iontr
ap m
ass spectrometer. The rel
ative drug form st
abilitiesin three different t
ablet formul
ations were differenti
atedusing this method; the s
alt-to-free
acid form conversionr
anged between less th
an the limit of detection to ne
arcomplete conversion during the st
ability study.