MEGLUMINE (Methylglucamine)

Limits of Nitrosamines
, ,
1

Hi!
someone is with the meglumine?
Meglumine (Methylglucamine) is an amino sugar derived from sorbitol.

NITROSO
image

1 Like
2

InChI=1S/C7H17NO5/c1-8-2-4(10)6(12)7(13)5(11)3-9/h4-13H,2-3H2,1H3/t4-,5+,6+,7+/m0/s1

image
image824Ă—426 14.9 KB

1 Like
3

Meglumine can form a nitrosamine-the nitrosomeglumine is commercially available.

3 Likes
4

Thanks to both of you!
The nitrosamine is commercially available. True!

  1. On the one hand, the problem is more analytical.
    I don’t know if anyone has evaluated the API/raw material content, being so polar it is a candidate for HILIC chromatography/ or sugar/amino column to try to retain and separate (even more so when using MS systems limited by volatile phase). I know that USP has a meglumine standard but I don’t know if this impurity is evaluated as such (or in the future).
  2. I also don’t know if anyone has evaluated the conversion rate of meglumine to nitrous. It may be a problem, if it is very favorable. I have seen that in the chemical industry it was eliminated as an intermediate for surfactants because nitrosamine should be formed very easily if there were unreacted remains.
  3. We lack data from some suppliers of this material when buying it.

Regards

5

Meglumine can nitrosate quite easily and you are right, @IreneNS , it is very difficult to analyze the hydroxy nitrosamines of this kind at low levels because they trail in the reverse phase LC and refuse to elute in many other column packing. especially trying to analyze small amounts is very tough due to trailing. I have faced this during my laboratory days. Try to see if you can derivatize the hydroxy groups in some way to stop the trailing. As they say, necessity is the mother of invention. Other option is as you said, to try some columns that are used traditionally for sugars to see how sensitive they are. Possibly you will be doing a lot of path finding work here :slight_smile: .

1 Like
6

Maybe @Aaron @Rajeshd @Adriana could suggest any resource for the challenge described above?

1 Like
7

Thank you very much for the reply.
I haven’t started the task yet, but I’m going to launch into asking lab vendors about the new columns. I have seen that Merck releases its coa with an amide ascentis for example… but I will ask if there are any news in columns (HILIC Sugar etc).
The problem is always the same for me. A client or authority asks the question and they give an absurd response time. There is no method and it looks horrible to set up a parsing method that works (and that we can leave for the batch release routine).
life is hard…

1 Like
8

Thank you!! As meglumine is at USP, one day, some of this will be included in their monograph.
So I think it’s interesting to think that it can work as a method… or that marketing people from large suppliers have it on their list of customer needs.
Greetings to all. :grinning:

2 Likes
9

Hi Naiffer,
We had success separating meglumine and the n-nitroso meglumine in HILIC mode using Luna Omega Sugar column.

Best,

Rajesh

6 Likes
10

Thank you for the information!! :smiley: You make me so happy. Thank you!

1 Like
11

Hi Rajesh can you please share the method we are very struggling the same method

12

Shall we apply NDSRI strategy for this impurity cause meglumine is to be used as excipient in the formulation drug products.

1 Like
13

Meglumine is commonly used excipient in the drug product formulations. Did anyone apply NDSRI strategy for meglumine nitrosamine impurity?

1 Like
14

yes I was apply NDSRI for your suggestion thank you.

15

Now AI of nitroso-meglumine is included in EMA appendix 1. 1500 ng/day is applicable based on negative bacterial reverse mutation test.

3 Likes
16

correct it was given under Telmisartan molecule

1 Like
17

Nitrosomeglumine is an excipient related nitrosamine. What MDD shall be considering for arriving at specifications? Is it drug substance label claim or corresponding Meglumine content in the formulation.

18

Hi Madhukar,
is your method related issue for nitroso meglumine solved? can you help me out with methodology or some sort of suggestions.

19

Hi, can you share the methodology or some useful tips on the method. i am developing the method for nitroso meglumine in one of the tablet formulation as meglumine is used as an excipient.