The Pros and Cons of Mass Spectrometry in the TDM Laboratory

The quantification of highly effective drugs in the setting of therapeutic drug monitoring is a great challenge for analytics. Low doses are usually sufficient for therapeutic success and plasma levels are expectedly very low. Determination with conventional HPLC-UV methods requires – provided that this is possible at all – a great temporal and technical effort. Fluorescence or electrochemical detectors are not usable in general or require long equilibration or conversion periods thus confining efficient and patient-oriented analysis.

Increase analytical requirements can be solved easily with coupling of HPLC to mass spectrometry. With tandem mass spectrometry, one can achieve an additional dimension of separation to the HPLC and therefore very high specifity simultaneously even with an almost universal and sensitive detector. In most cases, extraction and derivatization of samples is not necessary; thus sample preparation can be simplified and separation time can be shortened.

A general conversion of all HPLC methods to tandem mass spectrometry does not make sense. Both analytical and economic reasons can exclude the use of tandem-MS as a detection principle. Though there are robust ion-sources such as electrospray and APCI, the link between HPLC and the mass spectrometer represents still a possible source of error which should not be underestimated. Through matrix effects wrong results can be received by non compliance. The precision is about 2–3 per cent poorer against a well-established HPLC method. In individual cases it is possible to loose further analytical information due to the high specifity of the method.

Because the initial costs for a sophisticated LC-MS/MS instrument are about 10 times higher than for conventional HPLC equipment, the conversion is only useful with corresponding high sample numbers. In addition, the full potential of the method such as cost saving for sample preparation and time of analysis must be tapped. Up to about 200 samples can be processed with one instrument on one day which is equivalent to 3 to 4 HPLC instruments with appropriately more manpower requirement. Whether and which type of a LC-MS/MS instrument should be acquired for a TDM laboratory, must be decided individually. After implementation high development costs have to be considered. If then with own developments the problems of the method are imposed and could be mastered, it is likewise possible to establish new methods relatively quickly or adopt them to pre-existing procedures. At the moment 12 HPLC and 5 LC-MS/MS instruments are on duty in our laboratory. Solving present and future analytical challenges with an acceptable effort for method development is not imaginable in our laboratory without the LC-MS/MS technique.