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DMSO Will Ruin Your Platinum Drugs. Take Heed.

Here’s the sort of experimental detail that can destroy a whole project if you’re not aware of it. The platinum chemotherapy drugs are an odd class of things compared to the more typical organic compounds, but it’s for sure that many of the people using them in research aren’t aware of all of their peculiarities. One of those has been highlighted recently, and it’s a sneaky one.
DMSO is, of course, the standard solvent used to take up test compounds for pharmacological assays. It’s water-miscible and dissolves a huge range of organic compounds. Most of the time it’s fine (unless you push its final concentration too high in the assay). But it’s most definitely not fine for the platinum complexes. This paper shows that DMSO displaces the starting ligands, forming a new platinum complex that does not show the desired activity in cells. What’s more, a look through the literature shows that up to one third of the reported in vitro studies on these compounds used DMSO to dissolve them, which throws their conclusions immediately into doubt. And since nearly half the papers did not even mention the solvent used, you’d have to think that DMSO showed up a good amount of the time in those as well.
What’s even more disturbing is that these sorts of problems were first reported over twenty years ago, but it’s clear that this knowledge has not made it into general circulation. So the word needs to get out: never dissolve cisplatin (or the related complexes) in DMSO, even though that might seem like the obvious thing to do. Editors and referees should take note as well.

14 comments on “DMSO Will Ruin Your Platinum Drugs. Take Heed.”

  1. kjk says:

    Maybe good old soapy water would be good for solvating/emulsfying the molecules while still bieng close enough to the aqueous in vivo environment for an accurate simulation. Surely some surfactants are gentile enough to not break down cell membranes.

  2. Anonymous says:

    In my previous experience as a postdoc (heavy in using platinum compounds) we use phosphate-buffered saline, water, or saline as the vehicle, NEVER DMSO because of this exact reason. I am glad someone is spreading the word with a proper research study

  3. Simon Higgins says:

    I’m amazed no-one pointed this out earlier. Sulfoxides are pretty good ligands for Pt group metals, and they show interesting ambidentate chemistry (i.e. they can S- or O-donors, depending on the softness or hardness of the metal ion).

  4. Screend says:

    Interesting that the NSC supplies cisplatin in DMSO in its screening plates…

  5. Lewis Vidler says:

    This comes as no surprise to chemists. I pointed this out to my wife when I was an undergraduate and she was looking at cisplatin resistance. Showed her the literature and she subsequently used water (I think cisplatin was soluble enough in water for her experiment). She presented the data to her group and some of the more experienced researchers dismissed it saying “this is how we have always done things, why would we change now?”. Her supervisor took interest and I believed changed her practices.

  6. Anon says:

    As a biologist we always ran DMSO-only controls and on more than one occasion I saw a signaling response…so the other side of the fence has issues with it also.
    That also reminds me of all the MDs that would do cell culture experiments and use drug concentrations 10-10000 higher than than what the tumors experience in a patient/in the clinic. Yet the NIH kept feeding them “translational research” grants. :-/

  7. a. nonymaus says:

    This is why you hire inorganic chemists! Using DMSO as a solvent for Pt complexes is as much a blunder as deciding on nitrite or hypochlorite as the counter ion for a protonated primary amine.

  8. platinum_R_Us says:

    I grew up in a platinum-oriented cancer therapeutics lab about 25 years ago. A frustrating part of working in that field at the time was that different labs would routinely report wildly different results in purportedly similar models. DMSO undoubtedly contributed to that. It sounds like things have not improved in recent years.
    We never used DMSO, but didn’t like water much, either (because we did not want to immediately aquate the leaving groups). Instead, we reckoned that the most ‘relevant’ formulation to use in our preclinical work was the same stuff that patients would get. So, we bought clinical cisplatin through our pharmacy, reconstitited and used that.
    It’s surprising – and yet not – how often we forget or ignore details like this, but then wonder why no one’s data can be replicated.

  9. AnonyROS says:

    DMSO also interferes with some tox assays because of its ability to inhibit CYPs and to distort the effects of reactive oxygen species (ROS). You can be sure that a lot of historically accumulated tox data can be called into question because of this.
    Antioxidant properties of dimethyl sulfoxide and its viability as a solvent in the evaluation of neuroprotective antioxidants. J Pharmacological and Toxicological Methods 2011, 63, 209–215.
    EFFECTS OF ORGANIC SOLVENTS ON THE ACTIVITIES OF CYTOCHROME P450 ISOFORMS … DRUG METABOLISM AND DISPOSITION, 2001, 29(2), 141
    Assay System Reveals Modulation of Oxidative and Nonoxidative Glucose Metabolism due to Commonly Used Organic Solvents. Horm Metab Res 2008, 40, 29–37.

  10. The Iron Chemist says:

    Too many undergraduate and graduate students don’t realize the importance of inorganic chemistry. I’d like to say that it comes back to bite them in the rear, but their work is usually evaluated by other supposed experts who don’t sufficiently appreciate and understand the field.

  11. Anonymous says:

    Great, thanks for telling me. Now I’ll have to re-do all my doctorate research. At least four years down the drain. Tonight I’m going to slit my wrists.

  12. Anon says:

    Known 37 years ago.
    Solvolysis of cis – [Pt(NH,),Cl,] in Dimethyl Sulphoxide and Reactions of Glycine
    with [PtCl,(Me,SO)]- as Probed by ls5Pt Nuclear Magnetic Resonance Shifts
    and ls5Pt-15N Coupling Constants
    By S. JOHN S. KERRISONan d PETERJ. SADLER*
    J.C.S. CHEM. COMM., 1977: 861-863

  13. Yancey Ward says:

    I have often been surprised at the numbers of organic chemists I have run across over the years who don’t understand the nature of bonding in metal complexes.

  14. Academic111 says:

    The Sigma Product Info for cisplatin clearly states:
    “Even though cis-platin is soluble in DMSO, the use of
    DMSO to dissolve cis– or trans-diamminedichloroplatinum
    (DDP) in biological studies is strongly
    discouraged. The DMSO inserts itself into the ligand.”
    https://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Sigma/Product_Information_Sheet/1/p4394pis.pdf

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