........
.
NOTE DTZ (A) IS DILTIAZEM AND OTHER TWO ARE IMPURITIES
Structure elucidation of DTZ-II impurity
In the positive mass spectra, the protonated [M+H]
+ molecular ion was detected at m/z 370.1. The even m/z number of [M+H]
+
ions suggest that DTZ-II contains odd number of nitrogen atoms
(nitrogen rule). From these results the molecular ion of DTZ-II was
found to be at m/z 369. The mass difference between Diltiazem and DTZ-II
was found to be 45 amu less. The positive HR-MS spectrum showed
protonated molecular ion at m/z 370.1131 corresponding to molecular
formula C
20H
20NO
4S. When compared with the molecular formula of Diltiazem, there was a difference of C
2H
7N.
The difference can be rationalized in terms of the loss of trimethyl
amine moiety. The presence of additional aromatic signal at δ 7.55 ppm
in
1H NMR (Figure 9) and corresponding carbon signal at 131.741 ppm in
13C
NMR (Figure 10). The correlation between the carbon and proton clearly
observed in HSQC (Figure 11) and one methylene signal was observed in
HSQC. The methylene proton at
δ 4.38 and 4.71 ppm in
1H NMR corresponding carbon signal at 99.41 ppm in
13C
NMR. The aromatic methine proton at δ 7.55 ppm showed HMBC (Figure 12)
correlations for carbon C5 and C7 positions at 140.808 and 165.121 ppm
respectively (Figure 7). The aromatic methine proton at
δ 7.55 ppm showed correlation with methylene proton at
δ
4.38 and 4.71 ppm in COSY (Figure 13). NMR assignments are shown in
Table 1. The above spectral data supports the assigned structure as
2-(4-methoxyphenyl)-4-oxo-5-vinyl-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-3-yl
acetate (DTZ-II).
FOLLOW OTHERS IN .........http://www.orientjchem.org/vol31no3/analytical-characterization-of-two-new-related-impurities-of-diltiazem-by-high-resolution-mass-spectrometry-and-nmr-techniques/
Analytical Characterization of two new related
impurities of Diltiazem by High Resolution Mass spectrometry and NMR
techniques096
Jagadeesh Narkedimilli1,2,*, Y. Ravindrakumar1 ,Sandeep Mohanty1, T. Srinivasarao1, A. Jayashree2
1Dr. Reddy’s Laboratories Limited, API Plant-III, Medak District, Hyderabad 500072, Telangana, India.
2Centre for chemical sciences & Technology, Institute of
Science and Technology, Jawaharlal Nehru Technological University
Hyderabad, Kukatpally, Hyderabad 500085, Telangana, India.
Corresponding author E-mail:
jagadeeshn@drreddys.com
DOI : http://dx.doi.org/10.13005/ojc/310363
ABSTRACT:
Diltiazem (DTZ) is an optically active calcium channel blocker
having a benzodiazepine structure. Two impurities (referred as DTZ-I
and DTZ-II) were detected with area percentages ranging from 0.1% to
0.15% during the impurity profile study of Diltiazem hydrochloride drug
substance. A simple isocratic high performance liquid chromatographic
method (HPLC) and liquid chromatography–mass spectrometry (LC–MS) were
used for the detection. The impurities were isolated by preparative
column chromatography. Analytical information from nuclear magnetic
resonance and mass spectral data of the potential impurities revealed
their structures as
2-(4-methoxyphenyl)-5-methyl-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-3-yl
acetate (DTZ-I) and
2-(4-methoxyphenyl)-4-oxo-5-vinyl-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-3-yl
acetate (DTZ-II). Impurity identification, isolation and structure
elucidation were discussed.
KEYWORDS:
Diltiazem; Potential impurities; Isolation; characterization techniques
Copy the following to cite this article:
Jagadeesh N, Ravindrakumar Y, Mohanty S, Srinivasarao T, Jayashree A.
Analytical Characterization of two new related impurities of Diltiazem
by High Resolution Mass spectrometry and NMR techniques. Orient J Chem
2015;31(3).
//////////
DILTIAZEM IS
TAKE A TOUR
At Cape Agulus, Southern Most Tip In Africa, SOUTH AFRICA
At Cape Agulus, Southern Most Tip In Africa.
//////////////'
