⑔ጟ⋵଻ஜⅣႺ⎇ⓥᚲᐕႎ╙ 31 ภ㧘66 㧙 68㧘2004ේ⪺⺰ᢥஜᐽ㘩ຠਛߩ࡝ࠝ࠴ࡠ࠾ࡦ࠽࠻࡝࠙ࡓ෸߮࡟ࡏ࠴ࡠࠠࠪࡦ࠽࠻࡝࠙ࡓߩ

ಽᨆᴺ᫪↰㇌ᱜ㧘Ძ೑㓉⟤㧘ਛᎹ␞ሶㅒ⋧♽䈱㜞ㅦᶧ૕䉪䊨䊙䊃䉫䊤䊐䉕૶䈦䈩䋬ஜᐽ㘩ຠਛߩ࡝ࠝ࠴ࡠ࠾ࡦ࠽࠻࡝࠙ࡓ෸߮࡟ࡏ࠴ࡠࠠࠪࡦ࠽࠻࡝࠙ࡓߩಽᨆᴺࠍᬌ⸛ߒߚ㧚ஜᐽ㘩ຠਛߩ࡝ࠝ࠴ࡠ࠾ࡦ࠽࠻࡝࠙ࡓ෸߮࡟ࡏ࠴ࡠࠠࠪࡦ࠽࠻࡝࠙ࡓߪ 0.1
㧑㈶㉄ࡔ࠲ࡁ࡯࡞ࠍ↪޿ߡ᛽಴ߒ㧘࿕⋧᛽಴ᴺ(Bond Elut Certifyࠞ࡯࠻࡝࠶ࠫ)ࠍ↪޿ߡ㧘2 㧑ࠕࡦࡕ࠾ࠕ᳓-ࡔ࠲ࡁ࡯࡞ṁᶧߢࠢ࡝࡯ࡦࠕ࠶ࡊߒߚ㧚㜞ㅦᶧ૕䉪䊨䊙䊃䉫䊤䊐䈲䉦䊤䊛䈮 InertsilODS-3 (4.6 x 150 mm,5 µm)ࠍ㧘⒖േ⋧ߦ᳓㧦ࠕ࠮࠻࠾࠻࡝࡞㧦㈶㉄㧔650:350:5㧘v/v㧕ࠍ↪޿㧘᷹ቯᵄ㐳 230 nm ߢಽᨆߒߚ㧚
ᧄᴺߦࠃࠆஜᐽ㘩ຠ߆ࠄߩ࡝ࠝ࠴ࡠ࠾ࡦ࠽࠻࡝࠙ࡓ෸߮࡟ࡏ࠴ࡠࠠࠪࡦ࠽࠻࡝࠙ࡓߩ࿁෼₸ߪ 77 㨪82%㧘ቯ㊂ਅ㒢୯ߪ ࡝ࠝ࠴ࡠ࠾ࡦ࠽࠻࡝࠙ࡓ߇ 0.5 µg/g㧘࡟ࡏ࠴ࡠࠠࠪࡦ࠽࠻࡝࠙ࡓ߇ 0.7 µg/g ߢ޽ߞߚ㧚㨇ࠠ࡯ࡢ࡯࠼ :࡝ࠝ࠴ࡠ࠾ࡦ࠽࠻࡝࠙ࡓ㧘࡟ࡏ࠴ࡠࠠࠪࡦ࠽࠻࡝࠙ࡓ㧘HPLC㧘࿕⋧᛽಴ᴺ㧘ஜᐽ㘩ຠ㨉㧝⛯߇⍴޿߇㧔↢‛ቇ⊛ඨᷫᦼᣣએౝ㧕㧘⊒⃻߇ᣧߊ㧘ᵴߪߓ߼ߦ
࡝ࠝ࠴ࡠ࠾ࡦ࠽࠻࡝࠙ࡓ T Na ෸߮࡟ࡏ࠴ࡠࠠࠪࡦᕈ߽ TNa ߩ⚂୚ߢ޽ࠆ㧚TNa ߪೋ࿁㊂㨪Ǵg/day࠽࠻࡝࠙ࡓ T Na ߪวᚑ↲⁁⣼ࡎ࡞ࡕࡦߢ޽ࠆ㧚⊕⦡߆ࠄᛩਈࠍ㐿ᆎߒ㧘⛽ᜬ㊂㨪Ǵ g/day ߹ߢჇ㊂ߔ☳ᧃߢࠛ࠲ࡁ࡯࡞ߦ߿߿ߣߌߦߊߊ㧘᳓ߦ߶ߣࠎߤṁߌࠆ- 㧚૕ౝߩ TNa ߪ⚂㧑߇ T߆ࠄ Tߦ⣕࡛㧙࠼ൻ෻ߥ޿㧚᳓㉄ൻ࠽࠻࡝࠙ࡓ⹜ᶧ߿ࠕࡦࡕ࠾ࠕ⹜ᶧߦṁߌࠆ㧚ᔕࠍฃߌᵴᕈࠍ⊒⃻ߒ㧘↢‛ቇ⊛ඨᷫᦼ߇㨪ᣣߣ㐳޿㧚ൻቇᑼߪ TNa ߇ CHINNaO 㧔m w㧕㧘TNaⴊਛߩ↲⁁⣼ࡎ࡞ࡕࡦߩ㧑એ਄߇ࠣࡠࡉ࡝ࡦ߿ࠕ࡞ࡉ߇ CHINNaO 㧔mw㧕ߢ޽ࠆ-㧚࡝ࡦߣ⚿วߒ㧘⢄⤳ߢ࡛ࠫ࡯࠼࠴ࡠ࠾ࡦߦ⣕࡛㧙࠼ൻ㧘޽ࠆ޿ߪࠣࡠࠢࡠࡦ㉄෸߮⎫㉄ᛴว૕ߦઍ⻢ߐࠇ⢙᳝෸߮ᶖൻ▤ౝߦឃᴭߐࠇߚᓟ㧘⣺▤ᓴⅣߐࠇࠆ  㧚↲⁁⣼ࡎ࡞ࡕࡦߪೋᦼߦ⣢⤳߆ࠄឃᴭߐࠇ㧘⚿⣺ߦ㆐ߒߚᛴว
૕ߪ♮ਛߦឃᴭߐࠇࠆ㧚 T Na ߪࠨࠗࡠ࠾ࡦ㧘࠴ࡠ࠽ࡒࡦߩ⵾ຠฬߢǴ g ෸߮Ǵg ฽߹ࠇࠆ㍤೷߇⽼ᄁߐࠇ㧘࡝ࠝ࠴ࡠ࠾ࡦ࠽࠻࡝࠙ࡓ 60C

TNa ߪ࠴࡜࡯ࠫࡦ S ߩ⵾ຠฬߢ㍤ਛǴg ෸߮Ǵg ฽
߹ࠇࠆ㍤೷ߣ lg ਛǴg ฽߹ࠇࠆᢔ೷߇⽼ᄁߐࠇߡ޿ࠆ߇ 㧘⢈ḩߩᴦ≮ߩߚ߼ߦ૶↪ߐࠇࠆක⮎ຠߢߪߥ޿㧚TNa ෸߮ TNa ߩㆊ೾ᛩਈߦࠃࠅ㧘ᔃᖪ੣ㅴ㧘⣂ᜉჇട㧘ਇᢛ⣂㧘⁜ᔃ∝╬ߩᓴⅣེ∝⁁ 㧘ᝄᚢ 㧘ਇ⌁㧘㗡∩㧘߼߹޿㧘⊒᳨㧘␹⚻ㆊᢅ㧘⥝ᅗ㧘ਇ቟ᗵ㧘ば߁ߟ╬ߩ♖␹∝⁁㧘㘩᰼ਇᝄ㧘ཌྷฯ㧘ਅ∯╬ߩᶖൻེ∝⁁߿╭⡺∩㧘࡟ࡏ࠴ࡠࠠࠪࡦ࠽࠻࡝࠙ࡓ 60C᦬⚻㓚ኂ㧘૕㊀ᷫዋ㧘⣕ജᗵ㧘⊹⤏ߩầ⚃╬ߩ∝⁁߇⃻ࠇࠆߎߣ߇޽ࠆ㧚߹ߚ߹ࠇߦ⢄ᯏ⢻㓚ኂ߇޽ࠆ- 㧚TNa ෸߮ TNa ߪ⚵❱ߩၮ␆ઍ⻢ࠍჇᄢߐߖ㧘☼ᶧ᳓ஜᐽ㘩ຠਛߩ TNa ෸߮ TNa ߩಽᨆᴺߪႎ๔ߐࠇߡ޿

⣲㧘ࠢ࡟࠴ࡦ∛㧘↲⁁⣼ᯏ⢻ૐਅ∝㧘ᘟᕈ↲⁁⣼Ἳߩᴦߥ޿㧚TNa ෸߮ TNa ߩ᷹ቯᣇᴺߣߒߡㅒ⋧ࠞ࡜ࡓߣ⒖േ

≮⮎ߣߒߡㆡᔕߐࠇࠆ㧚TNa ߪೋ࿁㊂㨪Ǵ g/day ߆⋧ߦࠕ࠮࠻࠾࠻࡝࡞㧛᳓㧛࡝ࡦ㉄㧔:: v/v㧕  㧘ࠄ㐿ᆎߒ㧘㨪ㅳ㑆ߢẋᰴჇ㊂ߒ㧘⛽ᜬ㊂㨪Ǵ g/dayࠕ࠮࠻࠾࠻࡝࡞㧛᳓㧔 : v/v㧕  㧘ࡔ࠲ࡁ࡯࡞㧛᳓㧛ߣߔࠆ㧚 T Na ߪઁߩ↲⁁⣼ࡎ࡞ࡕࡦ⵾೷ࠃࠅലᨐߩᜬ

࡝ࡦ㉄㧔:: v/v㧕  ࠍ↪޿ߚ HPLC ᴺ߇ႎ๔ߐࠇ⑔ጟ⋵଻ஜⅣႺ⎇ⓥᚲ㧔‫⑔ ޥ‬ጟ⋵ᄥቿᐭᏒᄢሼะ૒㊁㧕ߡ޿ࠆ㧚ߒ߆ߒ㧘޿ߕࠇ߽㍤೷ߩ⹜㛎ᴺߢ޽ࠅ㧘ஜᐽ㘩ຠ㧟⚿ᨐ෸߮⠨ኤߦㆡ↪ߔࠆߦߪࠢ࡝࡯ࡦࠕ࠶ࡊᴺߩᬌ⸛߇ᔅⷐߢ޽ࠆ㧚㧟࡮㧝౒ሽ‛⾰ߩ㒰෰⹜ᢱ᛽಴ᶧਛߩ౒ሽ‛⾰ࠍ Bond Elut Certify ࠞ ࡯࠻࡝㧞

ታ㛎ᣇᴺ㧞࡮㧝࠶ࠫࠍ↪޿ߡ㒰෰ߔࠆᣇᴺࠍᬌ⸛ߒߚ㧚TNa ෸߮ TNaࠍߘࠇߙࠇǴg⹜⮎Bond Elut Certify ߦ ଻ᜬߐߖ㧘㧑ࠕTNa ෸߮ TNa ᮡḰේᶧߪ TNa㧔 Sigma ⵾㧕ࠍ

ࡦࡕ࠾ࠕ᳓ -ࡔ࠲ࡁ࡯࡞ṁᶧߩṁ಴㊂ࠍᬌ⸛ߒߚ㧚ߘߩmg㧘 TNa᳓๺‛㧔Sigma ⵾㧕ࠍmg ⒊㊂ߒ㧘%ࠕ

⚿ᨐ㧘㧑ࠕࡦࡕ࠾ࠕ᳓-ࡔ࠲ࡁ࡯࡞ṁᶧ㨪ml ߢߪ TNaࡦࡕ࠾ࠕ᳓ -ࡔ࠲ࡁ࡯࡞ࠍട߃ߡ ml ߣߒ಄ᥧᚲߦ଻

෸߮ T Na ṁ಴㊂ߪᷝട㊂ߩߘࠇߙࠇ㧑ߢ޽ߞߚ㧚ṁሽߒߚ㧚↪ᤨ㧘ᮡḰේᶧ㨪ml ࠍߣࠅ%ࠕࡦࡕ࠾ࠕ᳓-಴ᶧ㨪ml ߢߪߘࠇߙࠇ㧑෸߮㧑㧘㨪ml ߢࡔ࠲ࡁ࡯࡞ࠍട߃ߡml ߣߒߚ߽ߩࠍᮡḰṁᶧߣߒߚ㧚ߪ㧑෸߮㧑㧘㨪ml ߢߪߘࠇߙࠇ㧑㧘ṁ಴ᶧࡔ࠲ࡁ࡯࡞ߪ๺శ⚐⮎Ꮏᬺ㧔ᩣ㧕⵾ߩ HPLC ಽ ᨆ↪

㨪ml ߢߪ TNa ෸߮ TNa ṁ಴㊂ߪᷝട㊂ߩߘࠇߙࠇࠍ↪޿ߚ㧚࿕⋧᛽಴ߦߪ Varian ⵾ߩ Bond Elut Certify ࠞ㧑એਅߢ޽ߞߚ㧚ߎߩߎߣ߆ࠄࠢ࡝࡯ࡦࠕ࠶ࡊᠲ૞ᤨߦ࡯࠻࡝࠶ࠫ㧔LRC㧘mg㧘ml㧕ࠍ↪޿ߚ㧚߅޿ߡ㧘㧑ࠕࡦࡕ࠾ࠕ᳓ -ࡔ࠲ࡁ࡯࡞ṁ಴㊂ߪml ߣߒ㧑ࠕࡦࡕ࠾ࠕ᳓ -ࡔ࠲ࡁ࡯࡞ṁᶧߪࠕࡦࡕ࠾ࠕࠍ㧑ߚ㧚ታ⹜ᢱߩ᷹ቯᤨߦߪṁ಴ᶧࠍ⓸⚛ࠟࠬ᳇ᵹਅߢੇ࿕฽߻ࠕࡦࡕ࠾ࠕ᳓-ࡔ࠲ࡁ࡯࡞ṁᶧࠍ⺞ᢛߒߚ㧚ߒߚᓟ㧘㧑ࠕࡦࡕ࠾ࠕ᳓ -ࡔ࠲ࡁ࡯࡞ṁᶧࠍട߃ ml㧞࡮㧞ߦߒߚ㧚࿑ߦᮡḰṁᶧ෸߮ᷝട࿁෼⹜㛎ߢᓧࠄࠇߚஜⵝ⟎⚡ᄖๆశᐲᬌ಴ེ㧔 SPD- AV㧕෸߮࠺࡯࠲ಣℂⵝ⟎ᐽ㘩ຠ A ߩ HPLC ࠢࡠࡑ࠻ࠣ࡜ࡓࠍ␜ߒߚ㧚ߎߩࠢ࡝

㧔C-R A㧕ઃ HPLC ߪፉᵤ⵾૞ᚲ㧔ᩣ㧕⵾ߩ LCA ࠍ 㧘࡯ࡦࠕ࠶ࡊᠲ૞ߦࠃߞߡ౒ሽ‛⾰ࠍലᨐ⊛ߦ㒰෰ߔࠆߎࠞ࡜ࡓߪ GL ࠨࠗࠛࡦࠬ㧔ᩣ㧕⵾ߩ InertsilODS- 㧔ߣ߇ߢ߈ߚ㧚

mm㧘Ǵm㧕ࠍ૶↪ߒߚ㧚
㧞࡮㧟

ታ㛎ᠲ૞

㧞࡮㧟࡮㧝

60C෸߮60Cߩಽᨆᴺஜᐽ㘩ຠ g ࠍml ߩ⹜㛎▤ߦ⒊㊂ߒ㧘㧑㈶㉄ࡔ࠲ࡁ࡯࡞ml ࠍട߃㧘ಽ㑆ᝄߣ߁᛽಴ߔࠆ㧚 rpmߢ㆙ᔃಽ㔌ߒߚᓟ㧘ࡔ࠲ࡁ࡯࡞ጀࠍណขߔࠆ㧚ᱷᷲߦ㧑㈶㉄ࡔ࠲ࡁ࡯࡞ml ࠍട߃㧘ߐࠄߦ࿁᛽಴ߔࠆ㧚᛽಴ᶧࠍวࠊߖ㧘᳓ࠍട߃ߡ ml ߣߔࠆ㧚 BondElut

Certify ࠞ ࡯࠻࡝࠶ࠫ㧔 LRC mg  ml㧕ߦࡔ࠲ࡁ࡯
࡞ml㧘᳓ml㧘㈶㉄㧔ψ㧕ml ࠍ㗅ᰴᵹߒࠦࡦ࠺࡚ࠪ࠾ࡦࠣߔࠆ㧚᛽಴ṁᶧml ࠍ Bond Elut Certify ࠞ࡯࠻࡝࠶ࠫߦᵹߒ TNa ෸߮ TNa ࠍ଻ᜬߐߖߚᓟ㧘᳓࿑ᮡḰṁᶧ㧔#60C෸߮60Cฦ‫ޘ‬PI㧕෸߮ஜᐽ㘩ຠ# $ ߩ*2.%ࠢࡠࡑ࠻ࠣ࡜ࡓ

㧝㧘60C㧧㧞㧘60Cml ෸߮ࡔ࠲ࡁ࡯࡞ml ߢᵞᵺߔࠆ㧚㧑ࠕࡦࡕ࠾ࠕ᳓ ࡔ࠲ࡁ࡯࡞ṁᶧml ࠍᵹߒ TNa ෸߮ TNa ࠍṁ಴ߔࠆ㧚㧟࡮㧞

60C෸߮60Cߩ࿁෼₸ߣౣ⃻ᕈೋᶧml ࠍᝥߡ㧘-ml ࠍណขߔࠆ㧚ṁ಴ᶧߪ⓸⚛ࠟࠬᏒ⽼ߐࠇߡ޿ࠆஜᐽ㘩ຠ A ෸߮ B㧔⚊⼺⩶ࠍ฽᦭ߔ᳇ᵹਅ㨪͠ߢੇ࿕ߒ㧘㧑ࠕࡦࡕ࠾ࠕ᳓ -ࡔ࠲ࡁ࡯࡞ࠆ࠳ࠗࠛ࠶࠻↪ஜᐽ㘩ຠ㧕ࠍ↪޿ߡᷝട࿁෼⹜㛎ࠍⴕߞṁᶧml ࠍട߃㧘⹜ᢱṁᶧߣߔࠆ㧚ߚ㧚ஜᐽ㘩ຠ g ߦ TNa ෸߮ TNa ࠍߘࠇߙࠇǴgࠍᷝടߒታ㛎ᠲ૞ߦᓥߞߡ࿁෼₸ࠍ᳞߼ߚ㧚➅ࠅ㄰ߒታ㛎ߪ࿁ⴕ޿㧘ߘߩ⚿ᨐࠍ⴫㧝ߦ␜ߒߚ㧚㧞࡮㧟࡮㧞60C෸߮60Cߩ*2.%᷹ቯ᧦ઙ

ࠞ࡜ࡓInertsilODS-mmஜᐽ㘩ຠ A ߩ࿁෼₸ߪ T Na ߇㧑㧔㨪⒖േ⋧᳓㧛ࠕ࠮࠻࠾࠻࡝࡞㧛㈶㉄㧑㧕㧘TNa ߇㧑㧔㨪㧑㧕ߢ޽ߞߚ㧚ஜᐽ㘩㧔::㧘v/v㧕

ຠ B ߩ࿁෼₸ߪ TNa ߇㧑㧔㨪㧑㧕㧘TNaᵹ㊂

 ml/min߇㧑㧔㨪㧑㧕ߢ޽ߞߚ㧚ᄌേଥᢙߪ޿ߕࠇࠞ࡜ࡓ᷷ᐲ߽͠㧑એౝߢ޽ࠅ߶߷ḩ⿷ߔࠆ⚿ᨐࠍᓧߚ㧚ᧄᴺߦࠃࠆᵈ౉㊂ Ǵ lቯ㊂ਅ㒢୯ߪ TNa ߇Ǵg/g㧘 TNa ߇Ǵg/g ߢ޽ߞ᷹ቯᵄ㐳 nmߚ㧚ᧄᴺࠍ↪޿ߡ࠳ࠗࠛ࠶࠻↪ஜᐽ㘩ຠ⒳㘃ߦߟ޿ߡ଻ᜬᤨ㑆

TNa㧦ಽ㧘 TNa㧦ಽᔕ↪ߒߚ߇㧘޿ߕࠇ߽ᧂᬌ಴ߢ޽ߞߚ㧚⴫㧝ஜᐽ㘩ຠ߆ࠄߩ60C෸߮60Cߩᢥ₂ᷝട࿁෼⹜㛎⚿ᨐᣣᧄ⮎ዪᣇ⸃⺑ᦠ✬㓸ᆔຬળ㧦╙ᡷᱜᣣᧄ⮎ዪᣇ⸃⺑ᦠ㧘㧔ppC-㧕㧧 ᧲੩㧦ᑝᎹᦠᐫ㧘㧚

T3NaT4Na࿁෼₸ ± ᮡḰ஍Ꮕ**ஜᐽ㘩ຠ A*

76.7±3.077.8±1.9ஜᐽ㘩ຠ B*

81.2±4.1

81.7±4.1

ᣣᧄ⮎ዪᣇ⸃⺑ᦠ✬㓸ᆔຬળ㧦╙ᡷᱜᣣᧄ⮎ዪᣇ⸃⺑ᦠ㧘㧔ppC-㧕㧧 ᧲੩㧦ᑝᎹᦠᐫ㧘㧚
FDA Talk Paper on Unithyroid Approval

// 㧘- 

ᣣᧄක⮎ᖱႎ࠮ࡦ࠲࡯㧦ᣣᧄක⮎ຠ㓸㧧᧲੩㧦⮎ᬺᤨႎ␠㧘ஜᐽ㘩ຠ#෸߮$ߦ߅޿ߡ60C෸߮60Cߪᧂᬌ಴ߢ޽ߞߚ㧚

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Fukuoka Institute of Health and Environmental Sciences,Mukaizano 39, Dazaifu, Fukuoka 818-0135, JapanA reverse-phase HPLC method for determining liothyronine sodium (T3Na) and levothyroxine sodium (T4Na) in health foods
is described. T3Na and T4Na in health foods was extracted with 0.1% acetic acid in methanol. The sample solution for HPLC
was applied to solid phase extractions (Bond Elut Certify ) with 2% ammonium hydroxide in methanol as mobile phase. TheHPLC analysis was carried out on a column of InertsilODS-3 (4.6 x 150 mm, 5 µm) with H2O/CH3CN/CH3COOH㧔 650:350:5,v/v) as mobile phase and the eluate was monitored by UV detection at 230 nm. The recovery of T 3Na and T 4Na from the healthfood sample was 77-82%. The quantitation limits of this method of T3Na and T4Na were 0.5 and 0.7 µg/g, respectively.
[Key words; Liothyronine sodium, Levothyroxine sodium, HPLC㧘Solid phase extractions, Health Food]