The blood-brain barrier and triple quadrupole mass spectrometry

A major impediment to developing drugs that affect the brain, such as new treatments for Alzheimer’s Disease, Meningitis , Epilepsy, Parkinson’s disease and Multiple sclerosis, has been determining whether and how effectively a drug substance can cross the blood-brain barrier (BBB).  The barrier separates cerebrospinal fluid surrounding the brain from circulating blood and is highly selective in the molecules it lets through.  Physically, the barrier is created by “tight junctions between endothelial cells in CNS vessels that restricts the passage of solutes.”   The cells line some 400 miles of tiny capillary vessels throughout the brain. The barrier is neuroprotective and keeps out many common bacteria, but “In its neuroprotective role, the blood-brain barrier functions to hinder the delivery of many potentially important diagnostic and therapeutic agents to the brain. Therapeutic molecules and genes that might otherwise be effective in diagnosis and therapy do not cross the BBB in adequate amounts(ref).”

The blood-brain barrier stands in the way of new drug development(ref).  Specifically, most large-molecule drugs cannot pass through it, so testing the safety and efficacy of many possible new therapeutic agents for the brain poses a serious challenge.

Triple quadrupole mass spectrometry offers a way of working around this problem.  A triple quadrupole mass spectrometer is a sophisticated laboratory device about the size of a table-top refrigerator.  Technically, “A triple quadrupole mass spectrometer is a tandem mass spectrometer (TQMS) consisting of two quadrupole mass spectrometers in series, with a (non mass-resolving) radio frequency (RF) only quadrupole between them to act as a collision cell for collision-induced dissociation. The first (Q₁) and third (Q₃) quadrupoles serve as mass filters, whereas the middle (q₂) quadrupole serves as a collision cell(ref).”  

A TQMS can help determine exactly how much of a substance is getting through to the brain and is being used, for example, in research on drug treatments for Alzheimer’s disease.  As reported in the Aug 1 issue of GEN, “Another state-of-the-art tool, triple quadrupole mass spectrometry, gives scientists at Mithridion an advantage for working in the Alzheimer’s drug arena. Triple quadrupole mass spectrometry measures accurately and quantitatively small amounts of drugs in an extract of blood or brain tissue during preclinical studies. In Alzheimer’s disease research, it’s critical to confirm that new drug candidates are capable of crossing the blood-brain barrier to work in the brain. “The blood-brain barrier is quite an obstacle, and many drugs fail to get through,” Dr. Twose notes. — Not only does triple quadrupole mass spectrometry confirm that compounds enter the brain, but the technology also defines chemical structures required for this to happen. “We know many of the rules, so we can carry out an in silico process before we synthesize compounds,” continues Dr. Twose. Mithridion’s semi-rational approach to drug design provides a good estimate of whether compounds will pass into the brain, and triple quadrupole mass spectrometry verifies that this occurs(ref).”

The triple quadrupole mass spectrometer is an example of hundreds of new technologies that are helping accelerate the pace of medical and life sciences research and facilitating discoveries that will at some point allow us to live for centuries.  In proposing Giuliano’s Law which relates to the prospects for breaking through the 122 year human age limit, I asserted that improving technology was combining with several other factors to constantly accelerate the rate of discovery and availability of anti-aging interventions.  For a complete discussion of how these factors are combining to drive the acceleration, see the blog post Factors that drive Giuliano’s Law.  Finally if you want to get a sense of some of the other emerging technologies that are being put to work for life sciences discovery, development, and production, I suggest you browse through a copy of GEN (Genetic Engineering & Biotechnology News), a biotechnology industry trade newspaper-magazine.  Our daily newspapers are getting skinnier, but GEN seems constantly to be getting fatter.