Drug impurity profiling by capillary electrophoresis/mass spectrometry using various ionization techniques

Area of Science:

• Analytical Chemistry
• Pharmaceutical Analysis

Background:

• Capillary electrophoresis/mass spectrometry (CE/MS) is crucial for drug analysis.
• Electrospray ionization (ESI) is the dominant technique, but alternatives like atmospheric pressure chemical ionization (APCI), atmospheric pressure photoionization (APPI), and thermospray ionization (TSI) are emerging.

Purpose of the Study:

• To evaluate the suitability of ESI, APCI, APPI, and TSI for drug impurity profiling using CE/MS in positive ion mode.
• To compare the efficiency and detection limits of these ionization techniques for various drug impurities.

Main Methods:

• CE/MS analysis of carbachol, lidocaine, and proguanil with their potential impurities.
• Utilized ESI, APCI, APPI (with VUV lamp off for TSI) as ionization sources.
• Employed 100 mM acetic acid (pH 4.5) as the background electrolyte for separation.

Main Results:

• APPI produced both even- and odd-electron ions; others produced only even-electron ions.
• In-source fragmentation was highest with APCI and APPI.
• ESI and TSI achieved the best detection limits (100 ng/mL) for charged impurities.
• APPI and APCI ionized a wider polarity range but failed to detect quaternary ammonium compounds.
• Neutral impurities had detection limits around 500 ng/mL for ESI, APPI, and APCI.
• Impurity detection at 0.1% (w/w) was feasible with 1 mg/mL parent drug injection.

Conclusions:

• The tested CE/MS systems offer complementary information for drug impurity profiling.
• The choice of ionization technique depends on the polarity and nature of the impurities.
• Successful identification of an unknown carbachol impurity highlights the systems' utility.