Acetylsalicylic acid

Acetylsalicylic acid (Aspirin) belongs to a class of medications

known as non-steroidal anti-inflammatory drugs

(NSAIDs) and has been among the most popular medications

for treating mild to moderate pain. It also reduces

inflammation, clotting of blood, fever, redness, swelling

and discomfort caused by medical disorders such as

headaches, infections and arthritis.[1] Methimazole is used

to treat hyperthyroidism, a condition that occurs when

the thyroid gland produces too much thyroid hormone.[2]

Mass spectrometry has played a significant role in the

characterization and analysis of small molecules such as

Methimazole and Aspirin.[3,4] The present study was undertaken

to assess the structures and mechanisms of formation

of the principal fragment ions in the ESI mass spectra

of these two drugs. The CID mass spectra of Methimazole

and Aspirin and their corresponding deuterated analogs have

been studied in both the positive and negative ion modes.

Decomposition mechanisms are proposed for the principal

fragment ions using H/D exchange and the combination

of multiple-stage CID at low collision energy with

high-resolution mass measurements. The mass spectra of

Methimazole and Aspirin can serve as useful models for

structural determination of chemically or biologically

modified Methimazole/Aspirin or related compounds.

Acetylsalicylic acid were provided by Pfizer Global

Research and Development (Groton, CT). Ammonium-15N,

d4 deuteroxide solution, CD3OD, D2O and Acetic acid-d4

were purchased Sigma-Aldrich (St. Louis, MO). All chemicals

were used as received.

Sample preparation: Stock solutions of Methimazole

and Aspirin were prepared in HPLC grade methanol at

1.0 mg/mL. The stock solutions were then diluted with

mobile-phase from each solvent system to give a final

concentration of 20 μg/mL. No further sample preparation

was required.

Sample analysis: Infusion analyses were performed

on a TSQ Quantum Ultra AM triple-quadrupole mass

spectrometer (San Jose, CA). The solvent systems used in

this study were: A). 50:50 HPLC grade methanol and 0.1

acetic acid, B). 50:50 HPLC grade methanol and 50 mM

ammonium hydroxide, C). 50:50 HPLC grade methanol

and 0.1% Acetic acid-d4, and D). 50:50 HPLC grade

methanol and 50 mM Ammonium-15N, d4 deuteroxide.

All infusion studies were conducted using the instruments’

integrated syringe pump at a flow rate of 2.0 μL/min for

total of four minutes.

MS conditions: The TSQ Quantum Ultra AM was

calibrated in normal and high resolution modes with a

solution of 1,3,6-Polytyrosine. Accurate mass

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