Immunoassay is an examination method widely used in clinical testing. On the other hand, analysis method by mass spectrometry (MS) is a measurement technique which measures target components based on the mass of the components. The sample can therefore be distinguished from molecules having a similar structure such as metabolites. Especially, MS/MS analysis and MSn analysis are technologies which allow distinction of components having similar structures with high accuracy by converting target components to fragment signals. Mass spectrometry analysis method excels in selectivity and accuracy compared to the immunoassay method, and a movement of applying it to clinical examination is spreading.
Mass spectrometry analysis method can be applied to clinical examinations such as therapeutic drug monitoring (TDM) and metabolic disorder screening. One example of TDM is observing pharmacokinetics of drugs in human body. For administration of drugs to patients in medical sites, it is important to plan a dosing plan based on the symptom of each patient in order to ensure effectiveness and safety. Even if patients take the same amount of drugs, their therapeutic effects may differ. One reason for this is that the blood concentration of the drug in patients differs due to individual differences in drug pharmacokinetics. Therefore, one performs TDM, a technique of optimizing the dosage amount and dosage method by measuring the patient's blood concentration, so that it falls within a therapeutic range. For example, TDM is necessarily performed for immunosuppressants used to suppress rejection response to a transplanted organ. The therapeutic range of those immunosuppressants is in a low concentration range, from several ng/mL to several hundred ng/mL. When the patient's blood concentration of a drug exceeds the therapeutic range, a severe side effect such as hypertension, hyperglycemia, a peptic ulcer, or dysfunction of the liver or kidney may occur. In order to reduce such side effects, cocktail administration is generally performed, in which multiple types of immunosuppressants and a drug such as a steroid are administered while performing TDM.
Another known example is metabolic disorder screening in which whole blood is used as a specimen, and target components are extracted by liquid-liquid extraction to be measured by a mass spectrometer (Patent Document 1). Amino acids such as alanine and valine, and acyl carnitine are thus quantitated so as to examine the degree of the metabolic reaction of the target component in vivo.
The MS mode employed in the aforementioned two examples is the multiple reaction monitoring (MRM) mode of a triple quadrupole mass spectrometer which has high selectivity. MRM is a technique such that the first stage quadrupole functions as a filter to pass only the precursor signal through it, and the passed signal is cleaved in a collision cell so that only a product signal that is specific to the generated compound is monitored in the second stage quadrupole. In this method, a compound is examined by identifying it using mass information specific to the compound.
On the other hand, regarding the series of operations performed in a clinical application of mass spectrometry, although the device automatically analyzes samples, pretreatment of the samples are performed manually. A laboratory technologist needs to conduct a plurality of pretreatment processes using a plurality of devices, resulting in low efficiency. Therefore, there is a demand for a device that can efficiently perform a series of examinations so as to save labor, shorten the time for examination reporting, and downsize the device by integrating the components.
The substance to be examined may exist in a blood cell component or a serum/blood plasma component, and the specimen may be whole blood or serum/blood plasma, because the position of localization varies depending on the property of the substance to be examined. A pretreatment for whole blood is different from that for serum/blood plasma. Therefore, a device that can handle various examination items, that is, various pretreatments is demanded.
As an example of a technique capable of performing pretreatments on both whole blood and serum/blood plasma, there is a known device that can consistently perform immunoserological examination or biochemical examination which uses serum as a specimen, and blood coagulation examination which uses whole blood as a specimen (refer to, for example, Patent Document 2). The device performs the first half process of the biochemical examination or immunoserological examination in parallel with the process of the blood coagulation examination on the same examination area so that two types of examinations are performed consistently and efficiently.