PMID- 38093544
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231216
IS  - 1872-2059 (Electronic)
IS  - 1000-8713 (Print)
IS  - 1000-8713 (Linking)
VI  - 41
IP  - 12
DP  - 2023 Dec
TI  - [Chiral capillary gas chromatography for the separation of the enantiomers of 
      4-chloromethyl-2,2-dimethyl-1,3-dioxolane].
PG  - 1135-1140
LID - 10.3724/SP.J.1123.2023.06010 [doi]
AB  - Chiral compounds play an important role in the pharmaceutical industry owing to 
      their unique biological activities. The enantiomers must be separated because 
      they can exhibit different pharmacological activities. Thus, the development of 
      chiral separation methods is essential to determine the purity of enantiomers. 
      4-Chloromethyl-2,2-dimethyl-1,3-dioxolane is an important chiral pharmaceutical 
      intermediate. In this context, a method based on chiral capillary gas 
      chromatography was established for the separation and determination of the 
      enantiomers of 4-chloromethyl-2,2-dimethyl-1,3-dioxolane. The separation of (R)- 
      and (S)-4-chloromethyl-2,2-dimethyl-1,3-dioxolane was initially investigated 
      using two conventional stationary-phase capillary columns: SH-I-5Sil MS and 
      SH-WAX. The stationary phase of SH-I-5Sil MS consisted of 5% phenyl and 95% 
      polymethylsiloxane, whereas the stationary phase of SH-WAX consisted of 100% 
      crosslinked polyethylene glycol. Neither of the columns exhibited chiral 
      selectivity, so they both were unable to separate the enantiomers of 
      4-chloromethyl-2,2-dimethyl-1,3-dioxolane. Subsequently, the separation of (R)- 
      and (S)-4-chloromethyl-2,2-dimethyl-1,3-dioxolane was investigated using four 
      chiral columns: Rt-bDEXm, Rt-bDEXsm, Rt-bDEXse, and InertCap CHIRAMIX. Among the 
      chiral columns, Rt-bDEXse, which used a stationary phase composed of 
      2,3-di-O-ethyl-6-O-tert-butyl dimethylsilyl beta-cyclodextrin added to 14% 
      cyanopropyl phenyl and 86% dimethyl polysiloxane, achieved the best separation of 
      (R)- and (S)-4-chloromethyl-2,2-dimethyl-1,3-dioxolane. Thus, this column was 
      selected as the analytical column for further method optimization. Detection was 
      performed using a hydrogen flame ionization detector. The effects of various gas 
      chromatographic parameters, such as linear velocity, initial column temperature, 
      column heating rate, and solvent type, on the separation of (R)- and 
      (S)-4-chloromethyl-2,2-dimethyl-1,3-dioxolane were investigated. The optimal 
      chromatographic conditions included a linear velocity of 70 cm/s, an initial 
      column temperature of 70 ℃, and a column heating rate of 2.0 ℃/min. The final 
      column oven temperature was 150 ℃. Methanol, ethanol, ethyl acetate, n-hexane, 
      dichloromethane, and dimethyl sulfoxide were selected as solvents. The results 
      showed that dimethyl sulfoxide interfered with the peaks of the target compounds, 
      whereas the other solvents had no significant effect on the peak shape and 
      separation of (R)- and (S)-4-chloromethyl-2,2-dimethyl-1,3-dioxolane. Methanol 
      was finally selected as the solvent in this study. Further experiments revealed 
      that (R)- and (S)-4-chloromethyl-2,2-dimethyl-1,3-dioxolane could be rapidly 
      separated within 10 min, with a resolution greater than 1.5. A good linear 
      relationship was observed in the range of 0.5-50.0 mg/L, with a linear 
      correlation coefficient greater than 0.998. The limits of detection for (R)- and 
      (S)-4-chloromethyl-2,2-dimethyl-1,3-dioxolane were 0.07 and 0.08 mg/L, 
      respectively, and the corresponding limits of quantification were 0.22 and 0.25 
      mg/L, respectively. Spiked recovery tests were performed at three spiked levels 
      of 0.5, 2.0, and 10.0 mg/L using methanol as the blank to determine the accuracy 
      of the proposed method. The recoveries for (R)- and 
      (S)-4-chloromethyl-2,2-dimethyl-1,3-dioxolane were 94.0%-99.1% and 96.0%-98.8%, 
      respectively, with relative standard deviations (RSDs) of 1.26%-4.87% and 
      1.51%-4.46%, respectively. The established method is efficient and reliable; 
      thus, it can serve as a reference for the separation of the enantiomers of 
      4-chloromethyl-2,2-dimethyl-1,3-dioxolane. It can also potentially be applied to 
      evaluate the enantiomeric purity of other chiral compounds in the pharmaceutical 
      industry and produce chiral drugs and other related compounds.
FAU - Zhang, Zhenyong
AU  - Zhang Z
AD  - Shimadzu (Shanghai) Global Laboratory Consumables Co., Ltd., Shanghai 200233, 
      China.
LA  - chi
PT  - English Abstract
PT  - Journal Article
PL  - China
TA  - Se Pu
JT  - Se pu = Chinese journal of chromatography
JID - 9424804
SB  - IM
PMC - PMC10719802
OTO - NOTNLM
OT  - 4-chloromethyl-2,2-dimethyl-1,3-dioxolane
OT  - chiral separation
OT  - enantiomers
OT  - gas chromatography (GC)
EDAT- 2023/12/14 06:42
MHDA- 2023/12/14 06:43
PMCR- 2023/12/08
CRDT- 2023/12/14 02:05
PHST- 2023/12/14 06:43 [medline]
PHST- 2023/12/14 06:42 [pubmed]
PHST- 2023/12/14 02:05 [entrez]
PHST- 2023/12/08 00:00 [pmc-release]
AID - 10.3724/SP.J.1123.2023.06010 [doi]
PST - ppublish
SO  - Se Pu. 2023 Dec;41(12):1135-1140. doi: 10.3724/SP.J.1123.2023.06010.