PMID- 23146225
OWN - NLM
STAT- MEDLINE
DCOM- 20130718
LR  - 20121113
IS  - 1873-264X (Electronic)
IS  - 0731-7085 (Linking)
VI  - 72
DP  - 2013 Jan
TI  - Development and validation of RP-UPLC method for the determination of darifenacin 
      hydrobromide, its related compounds and its degradation products using design of 
      experiments.
PG  - 40-50
LID - S0731-7085(12)00521-3 [pii]
LID - 10.1016/j.jpba.2012.09.013 [doi]
AB  - A selective stability-indicating ultra-performance liquid chromatographic (UPLC) 
      method was developed for the quantitative determination of darifenacin 
      hydrobromide (DFN) and its related compounds in API and pharmaceutical dosages. 
      The chromatographic separation was achieved on an Acquity UPLC BEH C18 column 
      (100, 2.1 mm and 1.7 mum) at a flow rate of 0.3 mL/min, and detection was 
      performed at 210 nm. The typical retention behaviors of impurities at various pH 
      values were depicted graphically. The LC conditions were optimized by design of 
      experiments (DOE) to obtain optimal separation in the shortest possible run time. 
      A central composite design (CCD) was employed to study the main effects and 
      interactions of the independent variables. The drug and its thirteen impurities 
      were eluted within 13 min. The method exhibited consistent, high-quality 
      recoveries (93.8 +/- 2.1 to 99.8 +/- 1.5 (mean +/- RSD)) with a high precision for the 
      drug and impurities. Linear regression analysis revealed an excellent correlation 
      between peak responses and concentrations (R(2) values of 0.9991-0.9999) for the 
      drug and impurities. The stability-indicating capability of the method was 
      verified by forced degradation experiments and mass balance study. LC-MS revealed 
      protonated molecular ion peaks [M+H](+) at m/z 428.20, m/z 425.20 and m/z 281.30 
      for the acid (Imp-4), oxidized (Imp-6) and N-dealkylated (Imp-1) forms of DFN, 
      respectively. Possible degradation pathways were established based on the known 
      reactivity of the drug through hydrolysis, oxidation, N-dealkylation, phenyl 
      hydroxylation, dihydrobenzofuran ring hydroxylation and ring opening. The m/z 
      values of unknown degradation products were matched with the proposed structures 
      and reported DFN metabolites.
CI  - Copyright (c) 2012 Elsevier B.V. All rights reserved.
FAU - Murthy, M Vishnu
AU  - Murthy MV
AD  - Dr. Reddy's Laboratories Ltd, Active Pharmaceutical Ingredients, IPDO, 
      Bachupally, Hyderabad 500072, AP, India. vishnu.drl@gmail.com
FAU - Krishnaiah, Ch
AU  - Krishnaiah Ch
FAU - Srinivas, K
AU  - Srinivas K
FAU - Rao, K Srinivasa
AU  - Rao KS
FAU - Kumar, N Ramesh
AU  - Kumar NR
FAU - Mukkanti, K
AU  - Mukkanti K
LA  - eng
PT  - Journal Article
DEP - 20120924
PL  - England
TA  - J Pharm Biomed Anal
JT  - Journal of pharmaceutical and biomedical analysis
JID - 8309336
RN  - 0 (Benzofurans)
RN  - 0 (Pyrrolidines)
RN  - 0 (Solvents)
RN  - APG9819VLM (darifenacin)
SB  - IM
MH  - Benzofurans/*analysis/*chemistry
MH  - Chromatography, High Pressure Liquid/*methods
MH  - Drug Contamination
MH  - Drug Stability
MH  - Hydrogen-Ion Concentration
MH  - Hydrolysis
MH  - Mass Spectrometry/methods
MH  - Oxidation-Reduction
MH  - Pyrrolidines/*analysis/*chemistry
MH  - Solvents/chemistry
MH  - Technology, Pharmaceutical/*methods
MH  - Temperature
EDAT- 2012/11/14 06:00
MHDA- 2013/07/19 06:00
CRDT- 2012/11/14 06:00
PHST- 2012/03/14 00:00 [received]
PHST- 2012/09/09 00:00 [revised]
PHST- 2012/09/14 00:00 [accepted]
PHST- 2012/11/14 06:00 [entrez]
PHST- 2012/11/14 06:00 [pubmed]
PHST- 2013/07/19 06:00 [medline]
AID - S0731-7085(12)00521-3 [pii]
AID - 10.1016/j.jpba.2012.09.013 [doi]
PST - ppublish
SO  - J Pharm Biomed Anal. 2013 Jan;72:40-50. doi: 10.1016/j.jpba.2012.09.013. Epub 
      2012 Sep 24.