What was in the BIG box that arrived at LabSPACE Midrand?

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Nothing else than a new UPLC-LC-MS/MS with tandem PDA detection.  The new SHIMADZU 8045 offers everything LabSPACE requires in a robust and sensitive analytical, workhorse.

LCMS-8045 LIquid Chromatograph Spectrometer

What is the LCMS-8045 LIquid Chromatograph Spectrometer?

The LC-MS/MS is a powerful tool for the detection of residual chemical compounds, confirmatory identification of small organic molecules, and confirmation and quantitation of contaminants and adulterants in pharmaceutical, clinical, industrial and food samples.  Liquid chromatography–mass spectrometry (LC–MS) is an analytical chemistry technique that combines the physical separation capabilities of liquid chromatography (or HPLC) with the mass analysis capabilities of mass spectrometry (MS).

Our new toy includes a Nexara XR Binary Gradient UPLC with a PDA detector and Shimadzu LCMS-8045 Triple Quadrupole Ultra-Fast Mass Spectrometer (UFMS).  What impresses us about the SHIMADZU Mass Spectrometers are their ability to operate in both positive and negative ionisation mode, while analysing the same sample.  No requirements of chromatographic separation, saving time in method setup and validation.

LCMS is applied in many industries such as pharmaceuticals, biopharmaceuticals, forensic, industrial, food and environmental sector. For clinical research, the analysis of drugs, vitamins and minerals in whole blood, plasma, serum and urine is conducted routinely using LCMS.  Coupling of MS to chromatographic techniques has always been desirable due to the sensitive and highly specific nature of MS compared to other chromatographic detectors. 

Mass spectrometers operate by converting the analyte molecules to a charged (ionised) state, with subsequent analysis of the ions and any fragment ions that are produced during the ionisation process, on the basis of their mass to charge ratio (m/z). Several different technologies are available for both ionisation and ion analysis, resulting in many different types of mass spectrometers with different combinations of these two processes.  The most common ionization used is the electrospray ionisation (ESI) Source, capable of interfacing to LC and demonstrated its application to a number of important classes of biological molecules.  ESI works well with moderately polar molecules and is thus well suited to the analysis of many types of small molecules, pharmaceutical products, metabolites and peptides.

After Ionization, the molecules enter what is known as Quadrupole 1 (Q1).  A quadrupole analyser consists of a set of four parallel metal rods.  A combination of constant and varying (radio frequency) voltages allows the transmission of a narrow band of m/z values along the axis of the rods.  By varying the voltages with time it is possible to scan across a range of m/z values, resulting in a mass spectrum. The first and third quadrupoles are similar, but Ions can be induced to undergo fragmentation by collisions with an inert gas such as nitrogen or argon in the middle or second quadrupole (Q2), a process called collision induced dissociation.  The Q2 is a collision cell that has been designed to maintain the low pressure of the collision gas required for dissociation and transmit most of the fragment ions that are produced.  A particularly useful mass spectrometer configuration is obtained by placing a collision cell between two quadrupole mass analysers. This combination is called a triple quadrupole mass spectrometer and is an example of tandem MS in which two or more stages of mass analysis are independently applied

The advantage of tandem MS is the greatly increased specificity of the analysis over single stage mass analysis. For example, a compound of 400Da, producing a major M (H+) ion of 401 m/z during ESI fragments in Q2 to produce a major 383 m/z product ion.  Highly specific detection is achieved if the first and third quadrupoles are set to transmit ions of only 401 and 383 m/z respectively.  This technique is termed single reaction monitoring and the fragmentation is denoted 401>383.  Only analytes with this precursor/product ion combination will be detected.  In a complex biological sample there may be other components that produce a 401 m/z precursor ion during ESI but there is a low probability that they will also fragment to a 383 m/z product ion.  The retention time of the chromatographic peak is also unique and combining the LC with tandem mass spectrometer (LC-MS/MS) makes for a very selective and specific detection method.

It is generally difficult to perform quantitative determinations using absolute MS responses. This is because of the large number of factors that influence the absolute MS response such as the cleanliness of the ion source, ion optics and the collision cell, ion suppression, ion source flow rates, collision cell pressure and the ultimate MS vacuum. It is difficult to control all of these factors and, as a consequence, absolute MS responses are subject to significant day-to-day variation. Therefore, internal standards are usually required to achieve reliable and accurate quantitative results. Stable isotope versions of the analyte are ideal internal standards as they have almost identical chemical properties but are easily distinguished during MS.  Furthermore, they correct for any losses or inefficiencies in the sample preparation process and correct for ion suppression.

Applications.

PK analysis

Pharmacokinetics is the study of what the body does to the drug.  LC-MS has become the standard of analysing pharmaceutical compounds in complex biological matrixes.

PD analysis.

Pharmacodynamics is the study of what the drug does to the body.  Although ELISA assays used to be the go-to methods, LC-MS has been taking over this sector due to it’s lower cost and high selectivity in comparison with possible cross reactions in ELISA.

Pesticides

LC-MS can analyze a much wider range of chemicals than GC-MS. … The wide scope of pesticides covered and simple sample preparation is the key reason why liquid chromatography coupled to mass spectrometry is more and more frequently used for the detection, identification, and quantification of pesticides in food nowadays

Therapeutic Drug Monitoring and Toxicology;

Dissatisfaction with the high cost of commercial immunoassays used in therapeutic drug monitoring and their variable cross-reactivity with metabolites has spurred the development of LC-MS assays as alternatives.  The capacity to multiplex LC-MS assays so that several drugs and metabolites can be measured in one run is a useful feature of these assays, which can simplify laboratory workflows and provide additional pharmacokinetic information.

The use of LC-tandem MS for toxicology screening is attractive because of its potential, relative to GC-MS screening, to provide greater confidence in identifications, detect a wider range of drugs, toxins and their metabolites, and to simplify sample preparation.

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