Chemistry Reference
In-Depth Information
215.97
4.79
5.22
314.76
5.56
297.16
5.68
329.19
272.15
286.17
170.93
241.24
6×10
7
5×10
7
4×10
7
3×10
7
2×10
7
1×10
7
0
1.00
2.00
3.00
4.00
5.00
6.00
7.00
Minutes
FIgure 7.6
Extracted single quadrupole mass spectra from impurity peaks in a UHPLC
separation of ranitidine and related substances. Conditions: 2.1 × 100 mm, 1.7-µm C18 column,
50°C, 0.45 mL/min. UV detection at 230 nm, 1.0 µL injection. Mobile Phase A: 20 mM ammo-
nium bicarbonate pH 9.0, Mobile Phase B: Methanol. Gradient from 4% to 90% B in 7 min.
(
Source:
Figure courtesy of Waters Corporation.)
SIM result and used to identify some of the degradation products in an API, even at
trace levels.
Selective ion monitoring by LC/MS allows for the detection of single substances
as they elute, based on their mass-to-charge ratio and fragmentation pattern. This
tool gives the researcher a greater ability to detect peak inhomogeneity. For example,
very low-level impurities co-eluting with the API peak (with different masses and/or
fragmentation patterns) may be detected.
Once method specificity for the API and impurities has been established, method
specificity must be examined to ensure degradants are also well resolved. Success
with this part of the validation is needed to ensure the method will be stability
indicating. Typically, during stability testing, the API will partially degrade under
the more stressful (forced degradation) conditions (Section 7.3.1.1
)
. The interest-
ing part of this research is designing conditions that will only partially degrade the
API. This is where the analytical researcher has the opportunity to employ chemical
