DESC:he nitrosamine impurities namely NDMA, NDEA, NEIPA,
NDIPA and NPYL have been eluted with specific retention time to the extended of 30minutes
runtime as described in Figure-B
5 Procedure:
Using the above conditions, the sample is analysed and the nitrosamine impurities are quantified
against the respective standard and reported in ppm.
10 Example – 2 Quantification of N-Nitroso-N-methyl-4-aminobutyric acid (NMBA) in
Losartan Potassium by LCMS
Chromatographic conditions
The LCMS system used was LCMS-8060 triple Quadrapole Mass spectrometer coupled with
UHPLC system. The analytical column used in LCMS was Shim-pack C18 or equivalent as
15 specified with 150 mm x 4.6 mm, 5.0 µm, and gradient binary eluent of 0.1% v/v aqueous formic
acid and methanol with load volume of 10µl with concentration of 1000 x102 ppm in protic
solvent at 40°C.
Mass Spectrometer Parameter:
20
Above LC condition using MRM transition of ES technique with preconditioned 150°C of DL
and gas flow of 1.5 L/min. at 200°C of IT.
Procedure:
25 Using the above conditions, the sample is analyzed and the N-Nitroso-N-methyl-4-aminobutyric
acid are quantified against the respective standard and reported in ppm ,CLAIMS:We Claim
1. A method to quantify the content of nitrosamine impurities in ARB drugs wherein said
method comprises of:
5 a. providing a solution of ARB drug in a headspace vial using a diluent;
b. incubating the solution at a temperature in the range of 90 to 130°C;
c. chromatographic separation of nitrosamine impurities in a GC column; and
d. determining the concentration of each nitrosamine impurities by Mass
Spectrometer.
2. The method as claimed in claim1, wherein the diluent used for the GC analysis is low
boiling solvent, wherein the low boiling solvent has boiling point temperature below
95°C, selected from methanol, THF, ethanol, dichloromethane, dioxane, acetone and
acetonitrile.
3. The method as claimed in claim1, wherein nitrosamine impurities consisting of NNitrosodimethylamine (NDMA), N-Nitrosodimethylamine (NDEA) Nnitrosodiisopropylamine (NDIPA), N-nitrosoethyl isopropyl amine (NEIPA) and Nnitrosopyrrolidine (NPYL).
4. The method as claimed in claim1, wherein the Limit of Detection (LOD) and the Limit of
Quantification (LOQ) the method are 0.002?ppm and 0.008ppm respectively.
10 5. The method as claimed in claim1, wherein the length of the GC column ranges from 20-
70 m and selected from polar phase column like Carbowax 20M, which are based on
polyethylene glycol; and wherein, the gas chromatography column for the quantification
operate at a temperature range of 40-300°C.
6. The method as claimed in claim1, wherein the mass spectrometer is employed with a
triple quadrupole mass detector; wherein the mass detector is tuned for unit resolution in
mass range of 1 to 1000 Da by using per-fluoro tertiary butyl amine as reference for
calibration of masses; wherein, the mass detector is operated at a vacuum of about 10-511
Torr and temperature of ion source and interface is 150-300°C; and wherein, the
temperature of ion source and interface is about 250°