Evaluation of Analytical Methods for Pharmaceuticals and Personal Care Products

good morning I’m still morning I guess
I’ll a morning my name is Teresa ciao I’m the hplc group leader at wmse i will
also like to welcome you here to very happy to we have this symposium today
i’m going to talk about the evaluation of analytical method for pharmaceuticals
and personal care products and this is a very hot topic for the last seven years
old since the report from usgs but until we I’ve been interested in this for a
long time but until recently that about a year ago that we have bought the hplc
tandem mass spectrometry that can make it possible for us to look at the
analytical side of it because it will need a very high technology instrument
to do this a low level as you hear that most people are talking about
ppt level so for regular hplc would you with detection or anything
that you cannot go down to that level just some background on the
pharmaceutical and personal care for short PPC PS that they need it come from
the prescription and over counter drugs a lot of antibiotics hormones oestrogen
type of compound layer from birth control pills veterinary drug used a lot
from using on the life lifestyle animals I’ll pass and also seafood industry they
use a lot of antibiotic for raising seafood I stopped
eating stream because I found out that the shrimp nowaday has so much anybody and antibacterial software and
antibacterial microbial soap that we use daily PD now and from lesser extent from
cosmetic and neutrik quite vitamin type of thing the sources of this of course
mainly is come from the human activity from when we took the drug and then the
excretion and the usual that their compound the parent company and also
some metabolized through excretion to the wastewater treatment plant and also
don’t forget that a lot of people rush to the news medication down the toilet
it used to they tell people to do this this is not the right way to do
and also the disposal just can’t disposal into the garbage and residue
from how hospital in nursing home I assume most most of the antibiotic type
of compound veterinary drug used mainly the antibiotics and steroids that they
administered to animals like I said the seafood is another picnic area that I
heard about that the u.s. stop can refuse to import the shrimp from
Thailand because they found there’s so much high level or antibody in the
shrimp they use over there and I stopped waste from other cow horses and others
and waste is that they can go into the wash to the groundwater and cause now
the PPC be in the other in the jar service water the residue from
pharmaceutical manufacturing that I think this area is pretty well defying
control so that that is not the biggest point concern as we hear about studying
in nineteen late nineteen to 2000 year the usgs did a very national picture way
this away the 139 streams across 30 state which you include North East
Chicago you hear about that and they find that 80% of the water
sample contained the residues of PPC p of course we are talking about very low
ppb all pupici level parts per trillion level and there until reason we hear a
lot of talks about what’s the problem we find intersex seka fish in the Potomac
River they found out the mail carriers in the testers and then the research at
the great water greatly water Institute that Milwaukee they show that the lip at
all also called they they can cause the fish deposit fat into the eggs which is
it going to effective reproduction who knows although we may not see the fish
with so many hands yet but Bethenny is going to affect our waters system in our
small probably small Montreal human health one of the research need for this
area now the of course I come up with three areas just have to talk about the
monitoring survey you nearly know that’s why we had this symposium we want to
find out what kind work have done in our own state we had the north east chicago
area data from the USGS report and also I EPA now just can start doing
monitoring some they try to get some data in Chicago area and we also had the
central Illinois data from my cause data that we just heard about so I think as
there’s definitely more need for monitoring maybe in the southern
Illinois area that there’s more agricultural and farm use that we should
also monitor the stream over there for the analytical method would definitely
lit more laboratory that they can analyze these types of compounds at the
sub ppb level pippa ppt level right now there’s not so many laboratory can do
this nationwide and the laboratory laboratory they can
provide your car services that they charge close to a thousand
dollar per sample and also according to the chief of EPA and my mental science
section Christian Dalton he’s also recommend that we need a lot more
standardized methods for data comparison because now a lot of it a lot of data
being published your paper but there is what cat and dog sometimes you cannot compare them they are different there’s a lot of
issues you need in the quantitation method whether you’re using internal
standard external standard just as single item monitoring and lately the
heart the biggest thing they come up with the isotope dilution method for for
more accuracy so this is hard to compare the data and then another area
will be the pond saw study we how we don’t have a lot of data in that
in the wastewater treatment plants sometimes they most the
time the only sample water at the infra and efrain and compare the data
but where do they come from you in the urban environment do they come from my
knee hospital and nursing home for antibodies or or so we have some
more this hard data maybe we can do some kind p treatment before they get into
the wastewater to implant so that’s definitely there’s someone need for this
data and based on the mic hoist report that
since its kind he as he is a central Illinois area I have used that he’s
reporting come up with a list of target list that one day I show here
about 18 of them just represent and the Jesse anti inflammatory pain
killer type of thing so that’s the acid amides is lumina Finn are you poking
their processing type of compound and also caffeine everybody drink coffee
eaters we always find caffeine in the water we know that and anybody so from
superb fastest in choose trimethoprim these all these are different kinds of
antibody I can’t like to have a couple from rich family and antimicrobial we
know that with a charcoal cabin and try Coulson is being used in our cat daily
life nowadays and they are also find very company in the water and n-type
lipid a political it’s karim cabin Matheson is also being fun
quite prefect frequently in the water and and taxes cimetidine and ranitidine
I also add another compound is that is the entire lip academic is the
gemfibrozil just got add to that because a lot of people
are taking medication for the high collateral the method that we start evaluating is
based on the brand new US EPA Memphis 1694 it just got being published by US
EPA come out in December 2007 basically they have four methods for the groups of
the target analyzed using positive and negative ion most my goal is to try to
optimize it to use a little bit less a method for the list for the list that I
had about 20 20 of them I use a hplc waters symmetry column mousta the US EPA
method uses the 18 column I can’t went to a CA I like to have them come out
faster so I i use a city column we’re using the two mil elated milliliter ID
using a fro great upon 2 mil per minute and the mass mass spec that we had is
the water Michaelmas cultural micro tandem mass spectrometry we’re
happy to get that because then now we can do there msms work now the data i’m
going to present to you is the last two weeks that we start we’ll be
working on it me and my camera’s monte wilcoxon so the data you see is
just about two weeks work we’d study the softening in fact on on the illusion of
respond the USGS method they’re using a mixture of our methanol and as your
natural we know that most of most of these chemicals they are soluble make sure they are past sometimes they’re more soluble your methanol is
I’m moles better in as an HR so mostly we can take a look at it and we
find that as soon a trial isn’t probably not the best soften to use we got to
pick tend to be you have broader and methanol on the other hand is a gift the
best response and we had the biggest the highest peak height but the peaked
always tend to be more broader and so the mixture between the methanol and as
an HR seem to give the the night sister intermediary a good response but
also the pcat shopper and so this on one of the charcoal cabin and also the
another antibiotics so we decided to use the mixture of methanol and S&H are just
like us cpa and another thing we look also look at the desolvation gets in
fact we’re using nitrogen on the instrument to have remove the soften and
they call the desolvation gas and cannibalize the fro and then remove the
soften the less water to soften and as you can see that we were using from 250
to 750 and you see that the higher the flow rate the better the respond the
reason we did this tub has study is because one another’s sample try hykosan
in the published paper they said that the best full way they use these 250 and
so we did look at that 252 seem to give a little bit better respond but but then
for all the other PPC beads and the light we found that there 750 is better
so we will have to use 750 this is the method one basically using a
formic acid and ammonium formate buffer with the mixture of 5050 as a nitrile
methanol as you can see that we can look at eleven compound using this method
this is it has a mixture of a positive ion and negative an hour-ish woman you
can monitor the analyzed in both positive and negative i’m mode which is
nice the feature that we don’t have to run to run and you can cut
monitor both when they’re the first these are all the positive iron and we
also develop the collider we call the MLM method that from the parent iron to
a daughter iron so we monitor the daughter to the other apparently the
daughter and that will give you the highest sensitivity and this is the 20
PPP level which is very good i think we can go down definite can go down to two
PPP it seems to me and then with
the additional a thousand full of concentration from SPE solid-phase
extraction we can go to no pipe repair we know one or two cod4 p @ trillion
level and this is the other analyte that psycho chosen and try to get better now
with this method we put we had to attach your cycling you have here about the
family church hi colin is a is a family of antibiotic you actually has many many
rigors of them metabolized so he has published six or seven related compound
we had the tetracycline and the architecture chart cycling by this
method but we have no response from it so I and the literature say
that actually touches cycling as Patrick’s a sticky and dividing is tend
to stick to the to the Cylon all groups like glass and the column
inside that the backbone of the column is on low so they tend to stick to the
column and I think that that’s why we don’t have good response and the
USGS US EPA method actually has a method to their using instead of forming as
that they’re using off sounding asses so we try that it does show that
with the first two is the formic acid there’s no respond and then when we go
to the oxalic acid we had nice responsible for the analyte I’m still
working on it my rationale when I first think about as i said well maybe I add
the offside asset to the formic acid buffer and then maybe it will give me
the respond for the texture cycling but we already tried that it doesn’t seem to
work with the other pharmaceuticals and it seems to give a much lower response
for the other one by adding the acela acid the interesting thing is I also
found that or cell acids kiya not were not
very wallet oh it’s a lickin so maybe that’s why you have to touch your cycle
come out but it’s not volatile and using the electrospray you need
volatile compound you so if it is not volatile actually we eventually cause
poverty in the mass back in the MS region so I had to pick more
further look at it and then the method 3 and then another thing for a lot of this
a pink killers type I you Pavan naproxen and they don’t they don’t give a good
respond either with the formic acid the first method and so because when you
look at the structure they are woody like kabonk they had carboxylic
acid on it so it’s a organic acid and they tend to and this is the neck
defined mode so i think with the formic acid that with the low pH they have they
formed a potent a the compound so but for the neck of defiant you want to
remove the proton so it does not make a good iron respond for it that’s why we
had to switch to a water you instead of formic acid we just use water and that
give a higher pH and that tent that would give a very nice negative ion so
so for all these compounds there Jim ribose so this is the lower cholesterol
drug and I lab prof CNR Europe often they do well with just a water
instead of formic acid and we can also add the triangle cabana and the Tigers
on you into this method and so in a way if we had to use all these three method
then we just can’t run all the naked value by this method and the other first
method just run the positive ions so that would also give more sensitivity to
so this I think that’s it this is so far we have done so far for the
two week the next thing we have to do the we will try to do the solid phase
extraction to find efficient recovery efficiency as I mentioned earlier used
like I said the quantitation is a big problem for MSM
for LCM SMS whether you’re using the internal standard or the isotope
dilution method it makes a lot of differences in the quantitation um the
delusion I saw that the illusion seems to be the best method nowaday all the
paper come up using this technique but the problem is you all know that it’s
very expensive one isotope compound would cost at least $400
so you’re talking about 20 then you’re talking about $8,000 so
this is a big problem so that’s why most like even the US EPA method is using
just using internal standard so so that’s a that is a challenge we have to
overcome that you analyze this compound a very trailer and the question

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