Deeper Insight Into the Pyrolysis of Acetylsalicylic Acid by Means of Thermogravimetry and GC-MS, Part 1

  • GC-MS
  • STA
  • Pharma


Introduction In pharmacy, there is hardly any active ingredient about which more has been written than acetylsalicylic acid (or ASA for short; in English-speaking countries even the brand name Aspirin™ is often used as a synonym). Its success story began at the end of the 19th century when Dr. Felix Hoffmann synthesized the substance at the BAYER laboratories for the first time without impurities. Nowadays, it is still one of the most popular pharmaceu-ticals used across a broad therapeutic range. It belongs to the group of non-steroidal anti-inflammatory drugs (NSAIDs) and is indicated for the treatment of pain, fever and inflammation. In addition, it is used to prevent recurrence of heart attack or stroke in high-risk patients. In 1977, ASA was added as an analgesic to the “essential drug list” of the WHO (World Health Organization). [1]

This is one of four application notes that examine in more detail the thermal behavior of acetylsalicylic acid: Decomposition in different gas atmospheres, decomposition kinetics, and the resulting gas species. [2, 3, 4] 

Results and Discussion 

For the investigation of the thermal decomposition of acetylsalicylic acid, thermogravimetric measurements (TGA) were carried out with the NETZSCH STA 449 F3 Jupiter®, coupled to a GC-MS system (Agilent 8890 gas chromatograph and Agilent 5975 MSD). Inert gases such as helium were used as the purge gas atmosphere. Detailed information about the measurement conditions is summarized in table 1.

Table 1: STA measurement parameters

ParameterAcetylsalicylic Acid
Sample mass4.96 mg
CrucibleAl2O3, 85 µl, open
Temperature programRT to 50 °C, 10 K/min
Flow rate100 ml/min
Sample holderTGA, Type S

The pyrolysis of acetylsalicylic acid exhibits two mass-loss steps (see figure 1). The first mass loss of 66.4% is related to a peak in the mass-loss rate (DTG) at 170°C. The second mass-loss step amounts to 33.4% with a peak in the DTG curve at 327°C.

In order to provide insight into the pyrolysis products, the TGA-GC-MS coupling was used to separate the complex mixture of gases and to identify the different com-ponents. The measurement parameters for GC-MS are described in table 2.

1) Temperature-dependnt mass loss (TGA) and mass-loss rate (DTG) of acetylsalicylic acid in a helium atmosphere

Table 2: GC-MS measurement parameters

ParameterCryo Trapping Mode
ColumnAgilent HP-5ms
Column length30 m
Column diameter0.25 mm
Cryo trap-50°C, 45 min
Column diameter40°C, IsothermUntersuchungen bei geregelter und konstanter Temperatur werden als isotherm bezeichnet.isotherm, 48 min 40°C to 300°C, 15 K/min
Gas atmosphereHe
Column flow (split)2 ml/min (5:1)
ValveEvery 1 min

The gases released were sampled every minute on the cryo trap. After the thermogravimetric run, the cryo trap was heated from -50°C to 300°C at a heating rate of 300 K/min to vaporize the condensed compounds and let them separate over the GC column (which was heated at 15 K/min). This method increases the concen-tration of side products and enables excellent separation. The resulting total ion current is displayed in figure 2. Comparison of the detected MS spectra for each peak with the NIST library yields a number of compounds with excellent hit quality. Identification examples are shown for the peaks with a retention time of 59.31 min and 60.89 min in figures 3 and 4. Besides acetic acid, phenol, salicylic acid, and acetylsalicylic acid, cyclic oligomers of 2-hydroxy benzoic acid as stated in literature were also found. This analysis reveals that decomposition and evaporation take place simultaneously and furthermore explains why the two mass-loss steps are not separated. 

2) Chromatogram of the evolved decomposition products of acetylsalicylic acid collected by the cryo trap

Library Search

Retention time [min]NameHit quality
49.89Acetic acid91
56.63Acetic acid phenyl ester90
59.31 2-Hydroxybenzoic acid (= salicylic acid)97
60.89Acetylsalicylic acid81
62.94Phenyl salicylate95


(Dimer of 2-Hydroxybenzoic acid)

71.022,10,18-Trioxatetracyclo[,9).0(12,17)] tetracosa-1(24),4,6,8,12,14,16,20,22-nonaene-3,11, 19-trione (Trimer of 2-Hydroxybenzoic acid)90
3) Measured spectrum at 59.31 min (red, top) compared to the library spectrum of 2-hydroxybenzoic acid (blue, bottom)
4) Measured spectrum at 60.89 min (red, top) compared to the library specrum of aspirin (acetylsalicylic acid, blue, bottom)


The combination of thermogravimetry and GC-MS (gas chromatography / mass spectrometry) is a powerful tech-nique for gaining deep insights into thermal decompo-sition processes and the resulting gases released. The thermal decomposition of acetylsalicylic acid in a helium atmosphere results in a complex gas mixture of at least nine different compounds released. Previous studies by TGA-FT-IR  (Fourier transform infrared spectroscopy cou-pled to a thermobalance) showed that the first mass-loss step releases acetic acid and salicylic acid, whereas the second mass-loss step is the result of a complex decompo-sition reaction. The capability of GC-MS starts where FT-IR reaches its limitations and provides much deeper insights into mixtures of simultaneously released gases. TGA-GC-MS is capable to both separate and identify them.


  1. [1]
  2. [2]
    AN 209 – Deeper Insight into the Pyrolysis of Acetyl-salicylic Acid by Means of Kinetic Analysis, Part 2 
  3. [3]
    AN 210 – Deeper Insight into the Pyrolysis of Acetyl-salicylic Acid by Means of Thermogravimetric Measure-ments in Various Gas Atmopshere, Part 3 
  4. [4]
    AN 211 – Deeper Insight into the Pyrolysis of Acetyl-salicylic Acid by Means of Thermogravimetry and Mass Spectrometry, Part 4 
  5. [5]
    Gregory T. Long, Sergey Vyazovkin, Nicoleigh Gamble, Charles A. Wight, Journal of Pharmaceutical Sciences, Vol. 91, No. 3, March 2002 
  6. [6]
    AN 136 – About the Thermal Behavior of Acetyl- salicylic Acid and Aspirin