TSQ Quantum Discovery用APCI源快速定量分析培高利特

摘要：

Pergolide (Figure 1) is a synthetic ergoline derivative that is used for the treatment of Parkinson’s disease, providing therapeutic activity at doses as low as 0.75 to 3.0 mg per day. However, due to the severe side effects of pergolide treatment, therapy is often initiated at daily doses of only 0.05 mg.

The development of simple, fast, accurate, and precise methods for the determination of potent drugs, such as pergolide, requires ultimate performance from an analytical technique. Additionally, for a method to be of practical use for analysis following any given dosage, the method must have a broad dynamic range, preferably without detector saturation at higher analyte concentrations.

Although ESI has found widespread application in the development of sensitive detection methods for bioanalytical applications, it is more prone to matrix suppression than APCI and often requires longer chromatographic run times to compensate. In this study, the APCI source was used in combination with a relatively high chromatographic flow rate (0.8 mL/min) to assess the performance of the Thermo Scientific TSQ Quantum Discovery in the development of a sensitive detection method with an extremely short run time (~1 minute).

Additionally, the performance in the enhanced massresolution mode of the TSQ Quantum Discovery for the quantitative analysis of pergolide in plasma is tested. Utility of enhanced mass-resolution can achieve mass separation of an analyte of interest from isobaricmatrix/chemical interferences in the H-SRM experiment. This can result in a further improvement in quantitative performance for analytes present in complex biological matrices, and improved LLOQ (lower limit of quantitation) sensitivities relative to those obtained at unit mass-resolution. The increase in analyte sensitivity achieved using enhanced mass-resolution analysis is also accompanied by an extended linear dynamic range for these assays.

结论：

Highly satisfactory quantitative performance for pergolide in minimally-treated plasma is achieved by APCI/SRM on the TSQ Quantum Discovery using an extremely short run time. The criteria required for high throughput analysis of pergolide are, thus, accomplished by this method. In addition, the added sensitivity of the TSQ Quantum Discovery coupled with the extended linear dynamic range allows for the monitoring of low and high dose administration of this potent drug within the same assay. The enhanced mass-resolution feature of the TSQ Quantum Discovery provides the user a simple, yet rapid means to further improve method sensitivity and selectivity, without the need for additional sample manipulation.