Identification of Impurities in Norvancomycin Hydrochloride Drug Substance Using UHPLC-QTOF-MS.

RATIONALE: Norvancomycin (NVCM) hydrochloride belongs to a group of glycopeptide antibiotics and exhibits strong effects against Gram-positive cocci and bacilli. The safety of patients' lives is directly related to the quality of drugs. The impurities play often an important role in this process. This study aimed to investigate the impurity profile of NVCM hydrochloride.

METHODS

To identify the impurities, a simple and sensitive ultrahigh performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF-MS) method was developed. An ACQUITY UPLC BEH C18 column (2.1 × 100 mm, 1.7 μm) was used. The flow rate was set at 0.2 mL/min. Mobile phase (A) consisted of 10 mmol/L ammonium formate (pH 9.0) and mobile phase (B) was methanol. Gradient elution was performed as follows: 0-5 min, 15% B; 5-25 min, 15% B to 20% B; 25-40 min, 20% B to 70% B. Stress degradation experiments were conducted to check the specificity of the method.

RESULTS

Thirteen impurities and two degradation products were characterized using UHPLC-QTOF-MS.

CONCLUSIONS

Based on MS/MS spectral data and exact mass measurements, the chemical structures of the impurities were elucidated. This study provided a reference method for the quality control of NVCM hydrochloride.