DEGRADANT COMPOUNDIN A MEDICAMENT
`
`BACKGROUND
`
`[0001] The present invention relates to a degradant formed in a medicamentincluding at
`
`least carbachol and brimonidine, and more specifically to detecting improper storage by
`
`presence of the degradant compound.
`
`SUMMARY
`
`[0002] According to one embodimentof the present invention, a degradant compoundis
`
`disclosed. The degradant compound developsis in small, tolerable quantities when the
`
`medicamentis at room temperature conditions and increases over time and as the
`
`10
`
`temperature increases. Detection of the degradant compoundin specific quantities or
`
`detection of the degradant compound within a medicamentcan be indicative of detecting
`
`improper storage by presence of the compound. Methods of avoiding a degradation
`
`compound formation by storing at specific temperatures below room temperature can also
`
`be used.
`
`15
`
`DETAILED DESCRIPTION
`
`[0003]
`
`In a medicamentfor application to at least the eye that includesat least a
`
`combination of brimonidine and carbachol (Brimochol), a degradant chemical compound
`
`forms based on the time in storage and temperature in which the medicamentis stored.
`
`[0004] The degradant compound that developsis in small, tolerable quantities when the
`
`20
`
`medicamentis at room temperature conditions. The degradant compound develops in
`
`much greater quantities when the temperature increases andrises to intolerable levels for a
`
`user of the medicament. The degradant compound can serve as a marker for evaluating
`
`whether the medicamenthas been stored in the proper environmental conditions over time.
`
`[0005] An example of the degradant compoundis shown below and has a chemical name
`
`25
`
`of 2-((5-bromoquinoxalin-6-yl)amino)-4,5-dihydro-1H-imidazole-1-carboxamide.
`
`1 of 6
`
`
`
`Br
`
`Zo
`
`Z
`
`HN
`
`Chemical Formula: C,,H,, BrN,O
`Molecular Weight: 335.17
`
`[0006] A mechanism for the formation of the degradant compound from the brimonidine
`
`and carbachol of the medicament is shown below. The degradant compound can be
`
`formed by the lens modulation from lipoic acid choline due to the lipoic acid effect on
`
`reducing disulfide bonds.
`
`2 of 6
`
`
`
`Hyatt
`y
`
`:
`S
`NO FMy
`
`Bei
`ss:
`apenas ie
`x davraandslayed!
`
`
`
`Carbackol
`
`Choice
`
`Degradant
`
`[0007] The available 5 monthsof in-lab stability data for Brimochol within medicaments
`
`indicates a primary brimonidine degradant compound as shown above and observed in a
`
`brimonidine assay via method TRC-MTH-0066 at RRT=0.9. This degradant compoundis
`
`observed up to 3.3% at 40°C and up to 0.25% at 25°C after 5 months of storage. Table 1
`
`showsthe stability data.
`
`
`Time Point
`Storage Conditions
`
`25°C 40% RH
`
`40°C NMT 25% RH
`
`5 Months
`
`Initial
`
`0.09%
`
`0.09%
`
`
`1 Month
`0.13%
`0.47%
`
`2 Months
`
`0.15%
`
`0.74%
`
`
`3 Months
`0.15%
`1.1%
`
`Table 1
`
`3 of 6
`
`
`
`[0008] High resolution mass spectrometric HPLC-MSanalysis indicates the structure of
`
`the degradant compound as shown above.
`
`[0009] Detection of the degradant compoundin specific quantities or detection of the
`
`degradant compound within a medicament can be indicative of detecting improper storage
`
`by presence of the compound; and a methodof avoiding a degradation compound
`
`formation by storing at specific temperatures. Testing and detection can take place using
`
`various methods.
`
`[0010] Accordingly,it is to be understood that the embodiments of the invention herein
`
`described are merely illustrative of the application of the principles of the invention.
`
`10
`
`Reference herein to details of the illustrated embodimentsis not intendedto limit the
`
`scope of the claims, which themselvesrecite those features regarded as essential to the
`
`invention.
`
`4 of 6
`
`
