TY - JOUR
T1 - Development and application of a validated stability-indicating ultra-performance liquid chromatography (UPLC) method for the determination of dantrolene and its related impurities
AU - Tawakkul, Mobin A.
AU - Faustino, Patrick J.
AU - Sayeed, Vilayat A.
AU - Khan, Mansoor A.
AU - Khan, Saeed R.
PY - 2010/3
Y1 - 2010/3
N2 - A rapid, sensitive, and specific ultra-performance liquid chromatographic (UPLC) method was developed for the simultaneous determination of dantrolene and its potential degradation impurities. Chromatographic separation was achieved on a Waters Acquity UPLC system using a Waters BEH C18 (2.1 × 100 mm, 1.7 μM) analytical column and Waters BEH C18 (2.1 × 5 mm, 1.7 μM) guard column. The compounds were eluted with a linear acetonitrile gradient (25-75%) over 3 min with a buffer composition of sodium acetate for method development, quantitation, and forced degradation studies. The flow rate was maintained at 0.5 mL/min. Column temperature was maintained at 35°C. Injection volume was 4 μL, and analysis was detected by a photodiode array detector at 375 nm. The method was validated according to USP Category I requirements for dantrolene. Forced degradation of dantrolene was conducted under the conditions of hydrolysis, oxidation, photolysis, and stability-indicating UPLC method was developed and validated. Two degradation products (related compound B and C) were formed in 0.1 N NaOH and 0.1 N HCl, respectively. The dantrolene was stable to oxidative decomposition. The degradation behavior under UV light was similar to 0.1 N HCl conditions. The method was used successfully for the quality assessment of dantrolene and its three impurities.
AB - A rapid, sensitive, and specific ultra-performance liquid chromatographic (UPLC) method was developed for the simultaneous determination of dantrolene and its potential degradation impurities. Chromatographic separation was achieved on a Waters Acquity UPLC system using a Waters BEH C18 (2.1 × 100 mm, 1.7 μM) analytical column and Waters BEH C18 (2.1 × 5 mm, 1.7 μM) guard column. The compounds were eluted with a linear acetonitrile gradient (25-75%) over 3 min with a buffer composition of sodium acetate for method development, quantitation, and forced degradation studies. The flow rate was maintained at 0.5 mL/min. Column temperature was maintained at 35°C. Injection volume was 4 μL, and analysis was detected by a photodiode array detector at 375 nm. The method was validated according to USP Category I requirements for dantrolene. Forced degradation of dantrolene was conducted under the conditions of hydrolysis, oxidation, photolysis, and stability-indicating UPLC method was developed and validated. Two degradation products (related compound B and C) were formed in 0.1 N NaOH and 0.1 N HCl, respectively. The dantrolene was stable to oxidative decomposition. The degradation behavior under UV light was similar to 0.1 N HCl conditions. The method was used successfully for the quality assessment of dantrolene and its three impurities.
KW - Dantrolene
KW - Degradation
KW - Impurity
KW - UPLC
KW - USP related compound A, B, C
UR - http://www.scopus.com/inward/record.url?scp=77749316970&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77749316970&partnerID=8YFLogxK
U2 - 10.3109/10601331003623309
DO - 10.3109/10601331003623309
M3 - Article
AN - SCOPUS:77749316970
SN - 1060-1333
VL - 27
SP - 21
EP - 29
JO - Clinical Research and Regulatory Affairs
JF - Clinical Research and Regulatory Affairs
IS - 1
ER -