Technical Data. Analytical Data

Transcription

1 Technical Data Fast Method Scouting for Chiral Separation Utilizing CHIRAL ART s Chiral method optimization of ionic compounds utilizing immobilized type column in reversed phase mode Analytical Data -CBZ-DL-Alanine P. DL-Aoglutethimide P. Atropine P., 6 Benzoin P. 6,'-Binaphthyl-,'-diae P. 6,'-Binaphthyl-,'-diyl Bis(trifluoromethanesulfonate) P. 7,6-Bis(4-isopropyl--oxazolin--yl)pyridine P. 7,-Bis[(-methoxyphenyl)phenylphosphino]ethane P. 7,6-Bis(4-phenyl--oxazolin--yl)pyridine P. 8 Cetirizine (Levocetirizine) P. 8 Chloroquine P. 8 3,3'-Dibromo-,'-bi--naphthol P. 9 3,3'-Dibromo-,',6,6',7,7',8,8'-octahydro-,'-bi-- P. 9 aphthol,'-dimethoxy-,'-binaphthyl P. 9 Donepezil P. 9, Duloxetine hydrochloride P. Fenoprofen P. Flurbiprofen P. Hexobarbital P. Hydroxychloroquine P. Ibuprofen P.,'-Isopropylidenebis(4-phenyl--oxazoline) P. Ketae hydrochloride P. Ketoprofen P. Ketrolac P. Lansoprazole P. 3 DL-Mandelic acid P. 3 Metoprolol P. 3, 4 floxacin (Levofloxacin) P. 4 Phenoxybenzae P. 4 -CBZ-DL-Phenylalanine P. 4 Pindolol P. Propranolol P. Rabeprazole P. Sertraline hydrochloride P. 6 trans-stilbene oxide P. 6,,-Trifluoro--(9-anthryl)ethanol P. 6 Trimebutine P. 7 Troger s base P. 7 Valsartan P. 7 Verapamil P. 7 Warfarin P. 8 Zopiclone P. 8 Please see APPLICATI DATA SFC for applications of chiral compounds using SFC.

2 DAD E, Sig=344,6 Ref=4, (D: CHIRAL-SCREEIG SA-HEX- MTBE_HCQ SA3.D) DAD E, Sig=344,6 Ref=4, (D: CHIRAL-SCREEIG SB-HEX- MTBE- HCQC Q HEX_MTBE4.D) DAD E, Sig=344,6 Ref=4, (D: CHIRAL-SCREEIG SC -HEX- MTBE- HCQC Q HCQ_HEX-IPA-F8.D) DAD E, Sig=344,6 Ref=4, (D: CHIRAL-SCREEIG SA-HEX- MTBE_HCQ _4_SA.D) DAD E, Sig=344,6 Ref=4, (D: CHIRAL-SCREEIG SB-HEX- MTBE- HCQC Q _4_HEX_MTBE64.D) DAD E, Sig=344,6 Ref=4, (D: CHIRAL-SCREEIG SC -HEX- MTBE- HCQC Q _3_HCQ_HEX- ET- F8.D) DAD E, Sig=344,6 Ref=4, (D: CHIRAL-SCREEIG SA-HEX- MTBE_HCQ _8_SA37.D) DAD E, Sig=344,6 Ref=4, (D: CHIRAL-SCREEIG SB-HEX- MTBE- HCQC Q _8_HEX_MTBE43.D) DAD E, Sig=344,6 Ref=4, (D: CHIRAL-SCREEIG SC -HEX- MTBE- HCQC Q _7_HCQ_MTBE-IPA-F 8.D ) DAD E, Sig=344,6 Ref=4, (D: CHIRAL-SCREEIG SA-HEX- MTBE_HCQ _6_SA9.D) DAD E, Sig=344,6 Ref=4, (D: CHIRAL-SCREEIG SB-HEX- MTBE- HCQC Q _6_HEX_MTBE3.D) DAD E, Sig=344,6 Ref=4, (D: CHIRAL-SCREEIG SA-ACET-IPA- HCQC Q HCQ_ACET-IPA- F8.D) DAD E, Sig=344,6 Ref=4, (D: CHIRAL-SCREEIG SB-ACET-HC QCQ _3_H CQ_AC ET-IPA-F8.D) DAD E, Sig=344,6 Ref=4, (D: CHIRAL-SCREEIG SC -HEX- MTBE- HCQC Q HCQ_MTBE-ET-F8.D) DAD E, Sig=344,6 Ref=4, (D: CHIRAL-SCREEIG SC -ACET-HC QCQ _3_H CQ_AC ET-IPA-F8.D) DAD E, Sig=344,6 Ref=4, (D: CHIRAL-SCREEIG SA-ACET-HC QCQ _3_H CQ_AC ET-ET-F 8.D ) DAD E, Sig=344,6 Ref=4, (D: CHIRAL-SCREEIG SB-ACET-HC QCQ H CQ_AC ET-ET-F 8.D ) DAD E, Sig=344,6 Ref=4, (D: CHIRAL-SCREEIG SC -ACET-HC QCQ H CQ_AC ET-ET- F8.D) DAD E, Sig=344,6 Ref=4, (D: CHIRAL-SCREEIG SA-CH3C -HC Q HCQ- M_C-ET-F 8.D ) DAD E, Sig=344,6 Ref=4, (D: CHIRAL-SCREEIG SB-CH3C -HC Q HCQ- M_C-ET-F 8.D ) DAD E, Sig=344,6 Ref=4, (D: CHIRAL-SCREEIG SC -CH3C-HC Q HCQ-M_C-ET- F8.D) -... DAD E, Sig=344,6 Ref=4, (D: CHIRAL-SCREEIG SA-P-ET-H CQCQ HCQ_ME- ET -F8.D) DAD E, Sig=344,6 Ref=4, (D: CHIRAL-SCREEIG SB-P-H CQCQ _7_HCQ_ME- ET- F8.D) DAD E, Sig=344,6 Ref=4, (D: CHIRAL-SCREEIG SC -P-H CQCQ _7_HCQ_ME- ET -F8.D) Fast Method Scouting for Chiral Separation Utilizing CHIRAL ART s R43AE CHIRAL ART are HPLC columns with polysaccharide derivatives chiral selector, and are suitable for separations of wide range of chiral compounds. n CHIRAL ART Immobilized type with high solvent versatility, chromatographers can freely choose the most suitable mobile phase by considering the solubility and resolution of the target compounds. The excellent separation of various racemic compounds was achieved through fast method scouting utilizing the short columns and 3 µm CHIRAL ART immobilized type with three different chiral selectors. Method scouting Scouting protocol CHIRAL ART 3 μm, X 3. mmi.d. Amylose-SA Cellulose-SB Cellulose-SC P normal phase mode P 3 3 polar organic mode Mobile phase A B Additive 4 n-hexane MTBE ethyl acetate A acetonitrile methanol t-butyl methyl ether -propanol ethanol Gradient -% B B ethanol Gradient -% B Acidic compounds TFA, Acetic acid, Formic acid, etc. Basic compounds DEA, Butylae, Ethanolae, etc. Zwitterionic compounds Both or either of acidic additive and basic additive onionic compounds one 4 usually.% (upper limit.%) diethylae Experimental Matrix mode P P A n-hexane MTBE ethyl acetate acetonitrile methanol B -propanol ethanol -propanol ethanol -propanol ethanol ethanol ethanol additive.% DEA column Amylose-SA Select Cellulose-SC Cellulose-SB H Hydroxychloroquine : 3 µm, X 3. mmi.d. :.8 ml/ Gradient : %B (-. ), -%B (.-. ), %B (.-. ) for normal phase mode : %B (-. ), -%B (.-. ), %B (.-. ) for polar organic mode Temperature : : UV at 6, 9, 334 nm : µl ( mg/ml) The baseline resolution is achieved under four conditions in the method scouting for hydroxychloroquine. The combination of Amylose-SA phase and MTBE/ethanol containing.% DEA is selected as the most favorable condition in consideration of retention and resolution.

3 Separation results under simple isocratic conditions optimized through scouting of each compound The combination of the short columns packed with three types of 3 µm particles and the rapid gradient elution of eight types of ormal Phase (P) and Polar rganic (P) mobile phase are employed for separation method scouting of pharmaceutical compounds below. The selected conditions from scouting with gradient elution for each compound are convertedd to the isocratic elution methods and optimized. H S H Hydroxychloroquine meprazole Rabeprazole Lansoprazole Pindolol S H F F F S H H H Hydroxychloroquine α.6 Rs meprazole α.6 Rs.4 4 Rabeprazol α.8 Rs FD FJ F66G : CHIRAL ART Amylose-SA 3 µm, X 3. mmi.d. : A) MTBE/DEA (/.) B) ethanol/dea (/.) %B :.8 ml/ Temperature : : UV at 344 nm : µl ( µg/ml) : CHIRAL ART Amylose-SA 3 µm, X 3. mmi.d. : A) ethyl acetate/dea (/.) B) ethanol/dea (/.) %B :.8 ml/ Temperature : : UV at 9 nm : µl ( µg/ml) : CHIRAL ART Cellulose-SC 3 µm, X 3. mmi.d. : A) ethyl acetate/dea (/.) B) -propanol/dea (/.) %B :.8 ml/ Temperature : : UV at 9 nm : µl ( µg/ml) Lansoprazole α.7 Pindolol α 3. Pindolol (P mode) α.6 8 Rs. 4 Rs 4. 8 Rs FL FG FP : CHIRAL ART Amylose-SA 3 µm, X 3. mmi.d. Eluen : A) ethyl acetate/dea (/.) B) ethanol/dea (/.) %B :.8 ml/ Temperature : : UV at 9 nm : µl ( µg/ml) : CHIRAL ART Cellulose-SB 3 µm, X 3. mmi.d. : A) n-hexane/dea (/.) B) ethanol/dea (/.) 6%B :.8 ml/ Temperature : : UV at 6 nm : µl ( µg/ml) : CHIRAL ART Cellulose-SB 3 µm, X 3. mmi.d. : methanol/dea (/.) :.8 ml/ Temperature : : UV at 6 nm : µl ( µg/ml) DEA: diethylae The fast method development chiral separations is allowed through the method scouting. The selected conditions from scouting with gradient elution for each compound are converted to the isocratic elution methods and optimized to achieve the ultra-fast separation method within utes.

4 Chiral method optimization of ionic compounds utilizing immobilized type column in reversed phase mode ~ Influence of ph on retention behavior ~ Features of immobilized type columns F478AE Immobilized type CHIRAL ART columns can be used with various solvents that are commonly used for HPLC analysis. They can be used in both normal phase mode and reversed phase mode as they are compatible with non-aqueous and aqueous solvents (). Reversed phase mode will be effective in case where a sample is hydrophilic and has limited solubility in organic solvent (e. g. Hexane). In this technical data sheet, we will introduce influence of ph of mobile phase on retention behavior of ionic compounds. We also introduce several example of chiral separation on reversed phase mode. Specifications (Immobilized type) /Packing material Particle size (mm) CHIRAL ART Amylose-SA 3 CHIRAL ART Cellulose-SB CHIRAL ART Cellulose-SC Usable mobile phase ormal phase Reversed phase Chiral selector Amylose tris(3,-dimethylphenylcarbamate) Cellulose tris(3,-dimethylphenylcarbamate) Cellulose tris(3,-dichlorophenylcarbamate) Usable ph range.-9. Temperature range Pressure limit ~4 MPa n-hexane, n-heptane, methanol, ethanol, -propanol, acetonitrile, ethyl acetate, tetrahydrofuran, chloroform, t-butyl methyl ether, etc. acetonitrile, methanol, ethanol, -propanol, tetrahydrofuran, water, aqueous buffer, etc. Tips for optimizing chiral separation method of ionic compounds on reversed phase mode Mobile phase > ptimal ph that ionization of analyte is suppressed is recommended. (Retention will be extended and possibility of greater resolution is expected.) > Immobilized type CHIRAL ART columns are the best option. Reversed phase analyses with optimized separation methods Warfarin (pka.6) : CHIRAL ART Cellulose-SB : mm phosphoric acid (ph.)/ acetonitorile (/) F477A Donepezil (pka 8.6) : YMC CHIRAL Cellulose-SB : mm H 4 HC 3 -DEA (ph 9.)/ acetonitrile (4/6) F468A

5 Retention behavior of acid compound on reversed phase mode Influence of ph on retention behavior ph. ph _.D Warfarin (pka.6) : CHIRAL ART Cellulose-SB µm X 4.6 mmi.d. : mm phosphate buffer/acetonitrile (/) :. ml/ Temperature : : UV at 4 nm : µl (. mg/ml) 469_.D ph Retention of Warfarin ph 4.6 ph _.D 469_3.D Peak shape may deteriorated at around pka value of the compound Retention factor (k') 3... k' () k' () 46_.D ph ph 7. 46_4.D For acidic compound, retention is extended and good separation is achieved when decreasing the ph of a mobile phase (ionization was suppressed). Retention behavior of basic compound on reversed phase mode Influence of ph on retention behavior ph _.D Donepezil (pka 8.6) : CHIRAL ART Cellulose-SB µm X 4.6 mmi.d. : mm phosphate buffer/acetonitrile (4/6) :. ml/ Temperature : : UV at 4 nm : µl (. mg/ml) ph 6. Retention of Donepezil 47_.D 4. ph 7. ph 8. _4_467_6.D Retention factor (k') 3... k' () k' () ph 8.9 _3_467_3.D ph _6.D For basic compound, retention is extended and good separation is achieved when increasing the ph of a mobile phase (ionization was suppressed). 4

6 HPLC Analytical Data -CBZ-DL- アラニン -CBZ-DL-Alanine D89C -CBZ-DL- アラニン -CBZ-DL-Alanine V8E H α. Rs.4 4 L H α 3. L Rs 6.4 D D : CHIRAL ART Amylose-C eo ( µm) X 4.6 mmi.d. : n-hexane/-propanol/tfa (8//.) :. ml/ Temperature : : UV at 4 nm : µl ( mg/ml) : CHIRAL ART Cellulose-C ( µm) X 4.6 mmi.d. : n-hexane/-propanol/tfa (8//.) :. ml/ Temperature : : UV at 4 nm : µl ( mg/ml) DL- アミノグルテチミド DL-Aoglutethimide H78F アトロピン Atropine H38C CH3 H H78F α. Rs : CHIRAL ART Cellulose-SJ ( µm) X 4.6 mml.d. : n-hexane/ethyl acetate/diethylae (7//.) :. ml/ Temperature : : UV at 4 nm : µl ( mg/ml) : CHIRAL ART Amylose-C ( µm) X 4.6 mmi.d. : n-hexane/ethanol/ethanolae (87/3/.) :. ml/ Temperature : : UV at nm : µl ( mg/ml)

7 6 アトロピン Atropine H39C ベンゾイン Benzoin V9B CH3 H 6 α.93 Rs. 4 α.3 Rs : CHIRAL ART Cellulose-C ( µm) X 4.6 mmi.d. : n-hexane/ethanol/ethanolae (9//.) :. ml/ Temperature : : UV at nm : µl ( mg/ml) : CHIRAL ART Amylose-C ( µm) X 4.6 mmi.d. : n-hexane/-propanol (9/) :. ml/ Temperature : : UV at 4 nm : µl (. mg/ml) ベンゾイン Benzoin V8F,'- ビナフチル -,'- ジアミン,'-Binaphthyl-,'-diae E78V 7 4 (R)-(+) (R)-(+) H H H H (S)-(-) (S)-(-) 7 α.6 α.9 Rs. Rs : CHIRAL ART Cellulose-C ( µm) X 4.6 mmi.d. : n-hexane/-propanol (9/) :. ml/ Temperature : : UV at 4 nm : µl (. mg/ml) : CHIRAL ART Amylose-SA ( µm) X 4.6 mmi.d. : n-hexane/-propanol (/) :. ml/ Temperature : : UV at 4 nm : µl (. mg/ml) Sample : Supplied by Tokyo Chemical Industry Co., Ltd.

8 7,'- ビナフチル -,'- ジイルビス ( トリフルオロメタンスルホナート ),'-Binaphthyl-,'-diyl Bis(trifluoromethanesulfonate) E79B,6- ビス (4- イソプロピル -- オキサゾリン -- イル ) ピリジン,6-Bis(4-isopropyl--oxazolin--yl)pyridine E777B α. Rs.8 (R)-(-) (S)-(+) (R)-(-) (S)-(+) S CF 3 S CF 3 S CF 3 S CF 3 7 α.6 Rs 7.6 (R, R) (S, S) CH CH (R, R) CH CH (S, S) : CHIRAL ART Cellulose-SB ( µm) X 4.6 mmi.d. : n-hexane/methyl tert-butyl ether (/) :. ml/ Temperature : : UV at 8 nm : µl (. mg/ml) Sample : Supplied by Tokyo Chemical Industry Co., Ltd. : CHIRAL ART Cellulose-C ( µm) X 4.6 mmi.d. : n-hexane/-propanol (6/4) :. ml/ Temperature : : UV at 8 nm : µl (. mg/ml) Sample : Supplied by Tokyo Chemical Industry Co., Ltd.,- ビス [(- メトキシフェニル ) フェニルホスフィノ ] エタン,-Bis[(-methoxyphenyl)phenylphosphino]ethane T8B,-ビス [(-メトキシフェニル) フェニルホスフィノ ] エタン,-Bis[(-methoxyphenyl)phenyl-phosphino]ethane H78E α.9 Rs.9 PCH CH P 9 8 (R, R) (R, R) ma 7 6 (S, S) PCH CH P 7 4 (S, S) : CHIRAL ART Amylose-C eo ( µm) X 4.6 mmi.d. : n-hexane/-propanol (9/) :. ml/ Temperature : : UV at 8 nm : µl (. mg/ml) : CHIRAL ART Cellulose-SJ ( µm) X 4.6 mml.d. : n-hexane/chloroform (8/) :. ml/ Temperature : : UV at 9 nm : µl (. mg/ml)

9 ,6- ビス (4- フェニル -- オキサゾリン -- イル ) ピリジン,6-Bis(4-phenyl--oxazolin--yl)pyridine E78B セチリジン ( レボセチリジン ) Cetirizine (Levocetirizine) F4A 4 (R, R) α.3 Rs 3. (S)-Cetirizine (R, R) (S, S) (S, S) (R)-Cetirizine (Levocetirizine) α.7 Rs 9. : CHIRAL ART Cellulose-C ( µm) X 4.6 mmi.d. : n-hexane/ethanol (4/6) :. ml/ Temperature : : UV at 8 nm : µl (. mg/ml) Sample : Supplied by Tokyo Chemical Industry Co., Ltd. : CHIRAL ART Cellulose-C ( µm) X 4.6 mmi.d. : n-hexane/-propanol/formic acid/diethylae (7//./.) :. ml/ Temperature : : UV at nm : µl ( µg/ml) セチリジン ( レボセチリジン ) Cetirizine(Levocetirizine) F84C クロロキン Chloroquine F46C 6 H 3 4 (S)-Cetirizine (R)-Cetirizine (Levocetirizine) α. Rs.4 α.4 Rs : CHIRAL ART Cellulose-SB (3 µm) X 4.6 mmi.d. : acetonitrile/formic acid/diethylae (/./.) :. ml/ Temperature : : UV at nm : µl ( µg/ml) : CHIRAL ART Amylose-SA ( µm) X 4.6 mmi.d. : MTBE/ethanol/diethylae (9//.) :. ml/ Temperature : : UV at 344 nm : µl ( µg/ml) methyl tert-butyl ether 8

10 9 3,3 - ジブロモ -, - ビ -- ナフトール 3,3'-Dibromo-,'-bi--naphthol E78Q Br 3,3 - ジブロモ -,,6,6,7,7,8,8 - オクタヒドロ -, - ビ -- ナフトール 3,3'-Dibromo-,',6,6',7,7',8,8'-octahydro-,'-bi--naphthol E78S Br (S) (S) Br (S)-(-) (S)-(-) Br Br Br (R) (R)-(+) (R) Br Br (R)-(+) α.4 Rs.4 α.8 Rs : CHIRAL ART Amylose-SA ( µm) X 4.6 mmi.d. : n-hexane/ethanol (7/) :. ml/ Temperature : : UV at 8 nm : µl (. mg/ml) : CHIRAL ART Amylose-SA ( µm) X 4.6 mmi.d. : n-hexane/-propanol (7/) :. ml/ Temperature : : UV at 9 nm : µl (. mg/ml), - ジメトキシ -, - ビナフチル,'-Dimethoxy-,'-binaphthyl E78P ドネペジル Donepezil F34B (R) (S) (R) (S) α.3 Rs 4.7 α. Rs : CHIRAL ART Cellulose-SB ( µm) X 4.6 mmi.d. : n-hexane/-propanol (9/) :. ml/ Temperature : : UV at nm : µl (. mg/ml) : CHIRAL ART Cellulose-C ( µm) X 4.6 mmi.d. : n-hexane/ethanol/ethylenediae (8//.) :. ml/ Temperature : : UV at 7 nm : µl ( µg/ml)

11 ドネペジル Donepezil F477A デュロキセチン塩酸塩 Duloxetine hydrochloride F33A 4 H CH Duloxetine hydrochloride ((S)-Duloxetine hydrochloride) S H CH3 4 α. Rs 3. 4 Duloxetine related compound A ((R)-Duloxetine hydrochloride) S : CHIRAL ART Cellulose-SB ( µm) X 4.6 mmi.d. : mm H 4 HC 3 -diethylae (ph 9.)/acetonitrile (4/6) :. ml/ Temperature : : UV at 4 nm : µl ( µg/ml) : CHIRAL ART Amylose-C ( µm) X 4.6 mmi.d. : n-hexane/ethanol/diethylae (9//.) :. ml/ Temperature : : UV at nm : µl (. mg/ml) デュロキセチン塩酸塩 ( 米国薬局方記載条件 ) Duloxetine hydrochloride (The United States Pharmacopeia) F9A フェノプロフェン Fenoprofen V47B System suitability solution (. mg/ml Duloxetine hydrochloride,. mg/ml Duloxetine related compound A) 8 6 System suitability Result requirement Resolution (, ) Tailing factor (Duloxetine).8 ~.. Tailing factor (Duloxetine related compound A).8 ~.. H 4 α. Rs 3. S 4 Duloxetine hydrochloride ((S)-Duloxetine hydrochloride) H CH3 S Duloxetine related compound A ((R)-Duloxetine hydrochloride) V47B : CHIRAL ART Cellulose-C ( µm) X 4.6 mmi.d. : n-hexane/-propranol/diethylae (83/7/.) :. ml/ Temperature : 4 : UV at nm : µl (The United States Pharmacopeia 37th; Limit of Duloxetine related compound A) System suitability solution was prepared from duloxetine hydrochloride and duloxetine related compound A supplied as reagents for laboratory use. : CHIRAL ART Amylose-SA ( µm) X 4.6 mmi.d. : n-hexane/-propanol/tfa (9//.) :. ml/ Temperature : : UV at 4 nm : µl (. mg/ml)

12 フルルビプロフェン Flurbiprofen V47C ヘキソバルビタール Hexobarbital 6C α.3 Rs. 4 F V47C : CHIRAL ART Amylose-SA ( µm) X 4.6 mmi.d. : n-hexane/-propanol/tfa (9//.) :. ml/ Temperature : : UV at 4 nm : µl (. mg/ml) : YMC CHIRAL EA (R) X 4.6 mmi.d. : acetonitrile/water (/7) :.7 ml/ Temperature : ambient : UV at nm : µl (. mg/ml) ヒドロキシクロロキン Hydroxychloroquine F46A イブプロフェン Ibuprofen V4D 4 H α. Rs α.7 Rs. 6 4 V4D : CHIRAL ART Amylose-SA ( µm) X 4.6 mmi.d. : MTBE/ethanol/diethylae (9//.) :. ml/ Temperature : : UV at 344 nm : µl ( µg/ml) methyl tert-butyl ether : CHIRAL ART Cellulose-SB ( µm) X 4.6 mmi.d. : n-hexane/-propanol/tfa (99//.) :. ml/ Temperature : : UV at nm : µl ( mg/ml)

13 ,'- イソプロピリデンビス (4- フェニル -- オキサゾリン ),'-Isopropylidenebis(4-phenyl--oxazoline) T8F 塩酸ケタミン Ketae hydrochloride 6F CH CH C 3 C 3 H 4 4 (S, S). (S, S) (R, R) α 3. Rs 6.3 (R, R) : CHIRAL ART Amylose-C eo ( µm) X 4.6 mmi.d. : n-hexane/-propanol (7/) :. ml/ Temperature : : UV at nm : µl (. mg/ml) : YMC CHIRAL EA (R) X 4.6 mmi.d. : acetonitrile/. M a 4 (4/6) :. ml/ Temperature : ambient : UV at 68 nm : µl (.4 mg/ml) ケトプロフェン Ketoprofen V69K ケトロラック Ketrolac H78D α. Rs V69K : CHIRAL ART Cellulose-SC ( µm) X 4.6 mmi.d. : n-hexane/-propanol/tfa (9//.) :. ml/ Temperature : : UV at 4 nm : µl (. mg/ml) : CHIRAL ART Cellulose-SJ ( µm) X 4.6 mml.d. : n-hexane/tetrahydrofuran/tfa (7//.) :. ml/ Temperature : : UV at nm : µl (. mg/ml)

14 3 ランソプラゾール Lansoprazole F6B DL- マンデル酸 DL-Mandelic acid V97A F F F S H 8 7 H 6 4 α. Rs.4 α. Rs : CHIRAL ART Amylose-SA ( µm) X 4.6 mmi.d. : ethyl acetate/ethanol/diethylae (9//.) :. ml/ Temperature : : UV at 9 nm : µl ( µg/ml) : CHIRAL ART Amylose-C ( µm) X 4.6 mmi.d. : n-hexane/-propanol/tfa (8//.) :. ml/ Temperature : : UV at 4 nm : µl ( mg/ml) DL- マンデル酸 DL-Mandelic acid V97B メトプロロール Metoprolol H38D H H α.4 Rs α. Rs : CHIRAL ART Cellulose-C ( µm) X 4.6 mmi.d. : n-hexane/-propanol/tfa (8//.) :. ml/ Temperature : : UV at 4 nm : µl ( mg/ml) : CHIRAL ART Amylose-C ( µm) X 4.6 mmi.d. : n-hexane/ethanol/ethanolae (8//.) :. ml/ Temperature : : UV at 4 nm : µl ( mg/ml)

15 4 メトプロロール Metoprolol H39B オフロキサシン ( レボフロキサシン ) floxacin (Levofloxacin) F39A H H F 8 (S)-(-)-floxacin (Levofloxacin) 6 α.3 H F α. Rs. 4 Rs 4. (R)-(+)-floxacin : CHIRAL ART Cellulose-C ( µm) X 4.6 mmi.d. : n-hexane/ethanol/ethanolae (9//.) :. ml/ Temperature : : UV at 4 nm : µl ( mg/ml) : CHIRAL ART Cellulose-SC ( µm) X 4.6 mmi.d. : MTBE/ethanol/acetic acid/ethylenediae (//./.) :. ml/ Temperature : 4 : UV at nm : µl ( µg/ml) methyl tert-butyl ether フェノキシベンザミン Phenoxybenzae H77D -CBZ-DL- フェニルアラニン -CBZ-DL-Phenylalanine V43U 6 H 4 4 α.4 Rs.9 α.4 Rs 4.4 H77D3 KSJ V43U : CHIRAL ART Cellulose-SJ ( µm) X 4.6 mml.d. : n-hexane/ethanol/diethylae (9//.) :. ml/ Temperature : : UV at 7 nm : µl ( mg/ml) : CHIRAL ART Cellulose-SC ( µm) X 4.6 mmi.d. : n-hexane/-propanol/tfa (8//.) :. ml/ Temperature : : UV at 4 nm : µl ( mg/ml)

16 ピンドロール Pindolol F3C ピンドロール Pindolol F6A H H H H α. Rs 4. α. Rs : CHIRAL ART Cellulose-SB ( µm) X 4.6 mmi.d. : methanol/diethylae (/.) :. ml/ Temperature : : UV at 6 nm : µl ( µg/ml) : CHIRAL ART Cellulose-SB ( µm) X 4.6 mmi.d. : n-hexane/ethanol/diethylae (4/6/.) :. ml/ Temperature : : UV at 6 nm : µl ( µg/ml) プロプラノロール Propranolol V86A ラベプラゾール Rabeprazole F36A 4 H 4 S H α. Rs.6 α.9 Rs : CHIRAL ART Cellulose-C ( µm) X 4.6 mmi.d. : n-hexane/-propanol/diethylae (8//.) :. ml/ Temperature : : UV at nm : µl (. mg/ml) : CHIRAL ART Cellulose-SC ( µm) X 4.6 mmi.d. : ethyl acetate/-propanol/diethylae (9//.) :. ml/ Temperature : : UV at 9 nm : µl ( µg/ml)

17 6 セルトラリン塩酸塩 ( 欧州薬局方記載条件 ) Sertraline hydrochloride (The European Pharmacopoeia) (A) Reference solution (a) (6.8 mg/ml Sertraline for system suitability CRS) 7 (B) Test solution (6. mg/ml Sertraline hydrochloride) 7 E3C E36A (C) Reference solution (b) (.3 mg/ml Sertraline hydrochloride) E3A E36B Test solution and Reference solution were prepared from Sertraline hydrochloride supplied as a reagent for laboratory use. H H H Sertraline hydrochloride H H H Sertraline hydrochloride (enantiomer) : CHIRAL ART Amylose-C ( µm) X 4.6 mmi.d. : mixture /n-hexane (7/) :.4 ml/ Temperature : : UV at 7 nm : µl (The draft for The European Pharmacopoeia; Enantiomeric purity) n-hexane/-propanol/diethylae (97//) トランススチルベンオキサイド trans-stilbene oxide (+)-R,R-trans-Stilbene oxide,3,-tri-tert-butylbenzene (. mg/ml, t marker) : CHIRAL ART Amylose-C eo ( µm) X 4.6 mmi.d. : n-hexane/-propanol (9/) :. ml/ Temperature : : UV at nm : µl (. mg/ml) D89B (-)-S,S-trans-Stilbene oxide α 3. Rs 3.4 トランススチルベンオキサイド trans-stilbene oxide V8D トリフルオロアンスリルエタノール,,-Trifluoro--(9-anthryl)ethanol H78C 4 (+)-R,R-trans-Stilbene oxide 4 (-)-S,S-trans-Stilbene oxide α.3 Rs : CHIRAL ART Cellulose-C ( µm) X 4.6 mmi.d. : n-hexane/-propanol (9/) :. ml/ Temperature : : UV at nm : µl (. mg/ml) : CHIRAL ART Cellulose-SJ ( µm) X 4.6 mml.d. : n-hexane/tetrahydrofuran (9/) :. ml/ Temperature : : UV at 4 nm : µl (. mg/ml)

18 トリメブチン Trimebutine H77E トレガー塩基 Troger s base V63H α.3 Rs. 7 α.43 Rs H77E3 KSJ V63H.... : CHIRAL ART Cellulose-SJ ( µm) X 4.6 mml.d. : n-hexane/ethanol/diethylae (9//.) :. ml/ Temperature : : UV at 6 nm : CHIRAL ART Amylose-SA ( µm) X 4.6 mmi.d. : n-hexane/ethanol (9/) :. ml/ Temperature : : UV at 4 nm : µl (. mg/ml) バルサルタン ( 米国薬局方記載条件 ) Valsartan (The United States Pharmacopeia) E6B ベラパミル Verapamil V9D Test solution (. mg/ml Valsartan) H C H H 4 α.3 Rs 4. 7 Valsartan C H H 8 9 H E6B Valsartan enantiomer (Valsartan related compound A) : CHIRAL ART Cellulose-C ( µm) X 4.6 mmi.d. : n-hexane/-propanol/tfa (8//.) :.8 ml/ Temperature : : UV at nm : µl (The United States Pharmacopeia 34th; Related compounds) : CHIRAL ART Amylose-C ( µm) X 4.6 mmi.d. : n-hexane/-propanol/diethylae (9//.) :. ml/ Temperature : : UV at 4 nm : µl ( mg/ml) 7 Test solution was prepared from Valsartan supplied as a reagent for laboratory use.

19 8 ワルファリン Warfarin F468A ゾピクロン Zopiclone F79D Extracted ion chromatograms (m/z 389. > 4.) E7 Spiked hair (. ng/mg each) H (R)-Zopiclone α. Rs 7.3 Relative abundance 3 4 H (S)-Zopiclone (Eszopiclone) : CHIRAL ART Cellulose-SB ( µm) X 4.6 mmi.d. : acetonitrile/ mm phosphoric acid (/) :. ml/ Temperature : : UV at 4 nm : µl ( µg/ml) Courtesy of H. Miyaguchi, ational Research Institute of Police Science. J.Chromatogr. A 9 (7) -63. : CHIRAL ART Cellulose-SC (3 µm) X. mmi.d. : mm ammonium bicarbonate (ph 8. with aqueous ammonia)/acetonitrile (/7) :. ml/ Temperature : : ESI, positive : µl (Hair sample extracted by micropulverized extraction) Instrument : LC) Ultimate TM liquid chromatograph (Thermo Fisher Scientific) HRMS) Q Exactive TM mass spectrometer (Thermo Fisher Scientific)

20 89AE