instrumental analysis, we shall choose a reliable analytical procedure which
fulfils the requirements including specificity, sensitivity and accuracy. In pharmaceutical
analysis, liquid chromatography coupled with mass spectrometer (LC-MS) is
widely used. However, there are some errors introduced during the measurements
due to instability of the analytical instruments5.
Therefore, there is a need to develop methods for calibration to eliminate the
errors. In general, LC-MS system is calibrated in each batch analysis using a
variety of chemical standards4.
Instrumental performance is monitored through many indexes like retention time,
mass accuracy, limit of detection, repeatability, reproducibility, sensitivity,
etc. To ensure the mass accuracy of
mass spectrometer, some reference standards should be used regularly to
calibrate the mass shift, like CsI, tyrosine, peptide standard, etc. For some specific analysis like
parallel reaction monitoring (PRM), calibration of retention time of liquid
chromatography between runs could be conducted using specific calibration
standards, like iRT.6
ensure the stability of analytical system over a long period of time, quality
control charts (Shewhart charts) should be drafted to determine the above-mentioned
maintenance and cleaning are also required and mainly accomplished by professional
technicians or engineers from instrument manufactures.
3. Sample collection
samples are collected from different sources, including raw materials,
intermediate products, finished products and packaging materials, see Figure 1. In detail, the content of active
pharmaceutical ingredients (API) should be measured to ensure the quality of
the raw materials. Then samples collected from intermediate products are used
to monitor the production processes and optimize the procedure if necessary.
Finished products are collected for stability studies and microbiological
analysis. In addition, some packaging material should be sampled and then
ensured to be inert to the pharmaceutical components.