Toma Galaon, Jana Petre, Vasile Ion Iancu, Liliana Cruceru, Marcela Niculescu, Florentina Laura Chiriac, Diana Maria Puiu, Madalina Mihalache
Cytostatic drugs
Abstract:
A new sensitive and selective LC-MS/MS method with positive electrospray
ionization was developed to detect seven cytostatic drugs and one metabolite from
municipal waste water. The method separates the target analytes in only 16 minutes
using a Hypersil Gold column (100 x 2.1 mm, 3.0 µm) kept at 20°C and a mobile
phase made of aq. 0.2% HCOOH and ACN in the ratio 92/8 (v/v). A low mobile phase
flow of 0.2 mL/min was used to increase MS ionization yield and hence method
sensitivity. A complex two steps (10%/minute) and two plateau gradient elution
program was applied for 12 minutes to achieve analyte separation from matrix and
each other with highly efficient peaks. Collision energy, fragmentor and capillary
voltages were optimized to increase MS sensitivity. Optimization of LC-MS
parameters generated low instrumental LOQs situated in the range 0.1 ÷ 1.0 ng/mL.
MS detector response was linear between 1 and 100 ng/mL with R2 coefficients >
0.997 for all eight target analytes. SPE using Oasis HLB cartridges was employed to
concentrate target analytes from water samples with MeOH as elution solvent. Intraday and inter-day precision (RSD %) was situated between 5.4 ÷ 7.2% and 7.3 ÷ 10.8%, respectively. Cytostatics recovery after SPE was good due to internal standard
correction with values between 70 ÷ 134%. Overall method LOQs were situated
between 0.6 and 5.6 ng/L. The method was tested on four waste water samples from
a WWTP plant in Bucharest, but none of the targeted cytostatic drugs were found
above detection limit.
