Development and validation of a stability-indicating method for neostigmine bromide: separation, identification and characterization of degradation product using LC-MS and ESI-Q-TOF-MS/MS
By: Makkar, Rajan
.
Contributor(s): Singh, Jitender.
Publisher: Bangalore Association of Pharmaceutical Teachers of India (APTI) 2022Edition: Vol.56(4), Oct-Dec.Description: 1206-1218p.Subject(s): PHARMACEUTICSOnline resources: Click here
In:
Indian journal of pharmaceutical education and researchSummary: Objectives: Forced degradation study of the drug product and drug substance is very
much important in drug development and drug discovery to establish the intrinsic stability
and understand its behaviors towards different stress conditions. In the present work,
stress testing of neostigmine bromide (NBr) was carried out as per ICH guidelines to
identify and characterize the degradation product (DP) formed. Materials and Methods:
According to ICH guidelines, drug substance was subjected to various degradation
conditions. Waters BEH (Ethylene Bridge Hybrid) C-18 column (1.7 m, 100 mm 2.1 mm)
having the composition of mobile phase Eluent A: 0.01M KH2PO4 in water pH-2.5 with
orthophosphoric acid and Eluent B: Acetonitrile utilizing 220 nm wavelengths provided
the best separation of DP and drug component. Throughout the analysis, the injection
volume (5 μL) and flow rate (0.3 mLmin -1) were kept constant. Results: The limits of
detection (LOD) and quantitation (LOQ) were set at 25 ngmL-1 and 50 ngmL-1, respectively.
The method showed excellent linearity over a concentration range of 25-250 ngmL-1
with a regression coefficient (
R2) value of 0.9999. The results showed that significant
degradation was observed in base and oxidative degradation conditions whereas found
in neutral, acidic, photolytic and thermal degradation conditions. Conclusion: The DP was
identified and characterized using a sophisticated HRMS/MS/TOF approach for accurate
mass measurement using the ESI positive mode of ionization. In the present study, the
establishment of the degradation pathway of drug substance and fragmentation pathway
of DP-I were explained which was never reported in any literature.
| Item type | Current location | Call number | Status | Date due | Barcode | Item holds |
|---|---|---|---|---|---|---|
Articles Abstract Database
|
School of Pharmacy Archieval Section | Not for loan | 2023-0128 |
Objectives: Forced degradation study of the drug product and drug substance is very
much important in drug development and drug discovery to establish the intrinsic stability
and understand its behaviors towards different stress conditions. In the present work,
stress testing of neostigmine bromide (NBr) was carried out as per ICH guidelines to
identify and characterize the degradation product (DP) formed. Materials and Methods:
According to ICH guidelines, drug substance was subjected to various degradation
conditions. Waters BEH (Ethylene Bridge Hybrid) C-18 column (1.7 m, 100 mm 2.1 mm)
having the composition of mobile phase Eluent A: 0.01M KH2PO4 in water pH-2.5 with
orthophosphoric acid and Eluent B: Acetonitrile utilizing 220 nm wavelengths provided
the best separation of DP and drug component. Throughout the analysis, the injection
volume (5 μL) and flow rate (0.3 mLmin -1) were kept constant. Results: The limits of
detection (LOD) and quantitation (LOQ) were set at 25 ngmL-1 and 50 ngmL-1, respectively.
The method showed excellent linearity over a concentration range of 25-250 ngmL-1
with a regression coefficient (
R2) value of 0.9999. The results showed that significant
degradation was observed in base and oxidative degradation conditions whereas found
in neutral, acidic, photolytic and thermal degradation conditions. Conclusion: The DP was
identified and characterized using a sophisticated HRMS/MS/TOF approach for accurate
mass measurement using the ESI positive mode of ionization. In the present study, the
establishment of the degradation pathway of drug substance and fragmentation pathway
of DP-I were explained which was never reported in any literature.
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