Acrodisc MS Syringe Filters Used in a Clinical Test for Key Oncology Drug
Acrodisc syringe filters ensure sample purity in new rapid, quantitative method to assist clinicians with critical dosing decisions
October 7, 2021
In a continuation of our blog series looking at some of the ways Acrodisc® syringe filters are being applied by customers in their research, we review a recent publication1 from analytical chemists in the faculty of Pharmacy at Beni-Suef University in Egypt. The researchers describe the development of rapid, inexpensive methods for the quantitative characterization of a key immunology drug used in the treatment of prostate cancer.
Accurate measures of the levels of both the active pharmaceutical and its toxic metabolites are key drivers of the dosing decisions that physicians must make in order to balance the efficacy of the treatment against the discomfort and health of their patients. The researchers use Pall’s Acrodisc MS syringe filters during the purification of human clinical samples in order to ensure clean, accurate results that can be relied upon in a clinical setting, where inaccurate data could have very serious consequences.
Dosing is critical to balance efficacy and toxicity
The drug flutamide is an orally active anti-androgen used for the management of metastatic carcinoma, in particular the treatment of advanced prostate cancer. Unfortunately, like many oncology drugs, it has serious side effects that need to be managed. Chief amongst these is severe hepatotoxicity mediated by the drug’s toxic metabolites. Flutamide is metabolized by the liver into metabolites, several of which have significant toxicity. Two of the most important metabolites from a clinical perspective are flu-1 (4-nitro-3-(trifluoromethyl)phenylamine) and flu-3 (2-amino- 5-nitro-4-(trifluoromethyl)phenol). In their publication, the researchers detail a new method for the quantitative characterization of flutamide and its two key metabolites using HTPLC (high-performance thin-layer chromatography) and HPLC-DAD (high-performance liquid chromatography with diode array detection).
Drug and metabolite concentrations in clinical samples must be accurately determined
The ability to distinguish between the drug and its metabolitesis important clinically due to the difference in toxicity and pharmacokinetics. Flu-1 is the most important of the toxic metabolites of flutamide, it is the major hydrolytic degradation product of flutamide and consequently is present in higher levels than many of the other metabolites. Unfortunately, flu-1 also tends to remain at high levels in blood plasma and has been shown to cause severe hepatic dysfunction. By contrast, flu-3 is a relatively inactive metabolite and is easily excreted via the kidneys, representing 50-90% of the total metabolites in a patient’s urine.
Accurately determining the concentration of flutamide, flu-1 and flu-3 in clinical samples, such as blood and urine, enables physicians to determine the relative abundance of the pharmaceutically active flutamide, the deleterious flu-1, and the benign flu-3 in a patient’s body. The results of these blood and urine tests underpin dosing decisions that need to balance the desired pharmaceutical benefit against the damaging effects of the toxic metabolites.
Syringe filters ensure sample purity for accurate HPLC analysis
In the development of their methods,the researchers rely on Acrodisc MS syringe filters for two separate steps.
Firstly, for the preparation of human plasma samples for High-performance Liquid Chromatography (HPLC). The samples were precipitated using acetonitrile to remove any plasma proteins, vortexed, then centrifuged. The resulting supernatant was passed through a Acrodisc MS syringe filter [PN MS-3201] to eliminate any remaining protein or other impurities from the final mobile phase prior to HPLC.
Secondly, in the preparation of urine samples for both HPLC and High-Performance Thin-Layer Chromatography (HPTLC), the team prepared samples of human urine spiked with flutamide, flu-1, and flu-3 together with the appropriate solvents. These samples were again filtered using Acrodisc MS syringe filters [PN MS-3201] to ensure purity of the samples prior to analysis.
Figure 1: Acrodisc MS syringe filters. The Acrodisc MS syringe uses a water-wettable polytetrafluoroethylene membrane (WWPTFE) that is ideal for sample preparation. It offers extremely low extractable levels with good flow rates and retention efficiency.
The new methods can deliver results in under 10 minutes and with high accuracy, both important criteria for clinical lab tests. In addition, both methods were designed using the least hazardous solvents while delivering the highest chromatographic resolution, and both are far less costly than the current LC-MS methods in common use. Rapid results, low costs, and high accuracy give these new clinical tests clear utility in clinical practice.
Learn more about Acrodisc syringe filters, their applications, characteristics, and benefits on our website.
Pall Laboratory products are designed for professional laboratory applications only. This product is not approved for use in medical, clinical, surgical or other patient protection applications. It is also not suitable for use in Biopharmaceutical manufacturing or production.