HP Seq: Lys Recovery Problem (PDF Figs. Attached)

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Fellow HP Seqers:

In late February, we started noticing poorer-than-usual yield/recovery
of Lys and a slight reduction in RY using 3.1-based protein chemistry (ethyl
acetate solvent-based) on both of our HP sequencers (Enhanced G1005A). The
problem has also been observed in analyses of HSA bound to PVDF using 3.1
chemistry, but does not seem to be as pronounced in 3.5-based peptide
analyses (toluene/acetonitrile solvent-based). For the past couple of weeks,
the problem has become intolerable.

The RY plot for a 3.1-based 10 pmol HSA analysis in the first attached
figure demonstrates the problem. The 2 nmol HSA analysis in the same figure
does not show the problem, tending to indicate the presence of a trace
contaminant in one or more reagents or solvents.

Looking back at reagent/solvent changes associated with the Lys recovery
problem, R1 and S2A (ethyl acetate) stood out on the list. Using the same
3.1 analysis method, 10 pmol HSA samples were analyzed using (1) HP R1 & S2A,
(2) PE R1 (diluted to 3% PITC) & HP S2A and (3) PE R1 (diluted to 3% PITC)
and PE S2B (ethyl acetate for Procise 494). As can be seen in the second
figure, the substitution of PE S2B for HP S2A resulted in a profound
improvement in Lys recovery. Also observed using PE R1 was a 4-fold
reduction in DPTU as compared to HP R1 (data not shown). The lot #s involved
were HP-R1: 27-ke2x-kc, HP-S2A: 26-k7yz-k9, PE-R1: 9902020 and PE-S2B:
9902040 (Isn't it refreshing to see that PE still uses date-based lot numbers
like HP did a year ago?).

Although the substitution of PE R1 and S2B for the HP reagents markedly
improved the Lys recovery and appeared to have improved RY, the Lys yield is
still not as good as has been seen in past 10 pmol HSA analyses. Other HP
reagents may also have defects contributing to the Lys recovery problem. As
time permits, we will be making some home-brew R2 and testing its impact on
the problem.

Maybe the problem is just related to defective ethyl acetate. More
likely, the "dirty bottle" problem has reared its ugly head again and all HP
sequencer reagents and solvents are potentially at risk. "Dirty bottles"
contain particulate debris and, specifically, the plastic bottle coating that
is only supposed to be on the outside of the bottle, not on the inside. One
does not need to exercise one's imagination very much to envision which
chemically reactive plasticizers might be present in the coating. We
recently removed a bottle of S2A from one sequencer and found, after peeling
back the label, an inch-long plastic "booger" attached to the inside of the
bottle below the solvent line. Doesn't anyone look at these things before
filling them? Pathetic, pathetic, pathetic!

If you have recently observed the Lys recovery problem on your HP
sequencer or have identified a reagent or solvent associated with the
problem, please post the information so that we can all benefit from your
experiences.

Steve
====================
Stephen Tindall
Argo BioAnalytica, Inc.
====================

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