Water 18.2 mω

Methotrexate (purity ≥ 99%), phenacetin (purity ≥ 99%), castor oil, corn oil, mineral oil, olive oil, soybean oil, Cremophor^® EL, Span^® 80, Span^® 85, Tween^® 80, phosphate buffered saline (PBS), and hydrochloride (HCl) were purchased from Sigma-Aldrich (St. Louis, MO, USA). Labrasol^® was supplied by Daejung Chemicals & Metal Co., Ltd. (Siheung-si, Gyeonggi-do, Republic of Korea). Ethanol and sodium chloride (NaCl) were purchased from Duksan (Ansan-si, Gyeonggi-do, Republic of Korea). LC-MS grade methanol, acetonitrile, water (18.2 mΩ), and HPLC-grade ethyl acetate were obtained from Fisher Scientific (Fair Lawn, NJ, USA). LC-MS grade formic acid was supplied by Tokyo Chemical Industry (Tokyo, Japan). All other reagents used for the experiments were in analytical grades.

The reference standard for ephedrine (purity ≥ 99%; CAS Number: 299-42-3) was purchased from Sigma-Aldrich (St. Louis, MO, USA). The reference standards for cinnamic acid (purity ≥ 98%; CAS Number: 140-10-3) and paeoniflorin (purity ≥ 98%; CAS Number: 23180-57-6) were obtained from the National Development Institute of Korean Medicine (Jangheung-gun, Jeollanam-do, Republic of Korea). Diphenhydramine hydrochloride (purity ≥ 99%; CAS Number: 147-24-0) and geniposide (purity ≥ 98%; CAS Number: 24512-63-8) as an internal standard (IS) were purchased from Sigma-Aldrich. Figure 1 shows the structure of cinnamic acid, paeoniflorin, ephedrine, and the IS. Liquid chromatography–mass spectroscopy (LC-MS)-grade acetonitrile, methanol, water (18.2 mΩ), and high-performance liquid chromatography (HPLC)-grade ethyl acetate were purchased from Fisher Scientific (Hampton, NH, USA). LC-MS-grade formic acid and acetic acid were supplied from Sigma-Aldrich. All other reagents were in the highest HPLC grades or quality available. Heparin sodium (25,000 IU/5 mL) was purchased from JW Pharmaceutical Corporation (Seoul, Republic of Korea). The SCRT tablets (manufacturing date: 10.01.2017; manufacturing number: H71501502) used in this study were supplied from Kyung-bang Pharmaceutical Company (Incheon, Republic of Korea).

MTX (purity ≥ 99%), PLGA with a molecular weight 30,000–60,000 g/mol, PVA with molecular weight of 31,000–50,000, phosphate buffered saline (PBS), DHF (purity > 90%) and THF (purity > 90%) were purchased from Sigma-Aldrich (St. Louis, MO, USA). UPLC-MS/MS grade methanol, acetonitrile, water (18.2 mΩ), and HPLC grade ethyl acetate were purchased from Fisher Scientific (Fair Lawn, NJ, USA). UPLC-MS/MS grade formic acid was supplied by Tokyo Chemical Industry (Tokyo, Japan). All other reagents and solvents were in analytical grades.
Roswell Park Memorial Institute (RPMI) 1640 medium and Trypsin-EDTA were obtained from Welgene Inc. (Gyeongsan-si, Republic of Korea). Fetal bovine serum (FBS) was supplied from Merck Millipore (Burlington, MA, USA). Penicillin/streptomycin was purchased from Thermo Fisher Scientific (Waltham, MA, USA). Trypan blue was purchased from Sigma-Aldrich (St. Louis, MO, USA). MCF-7 cells were purchased from Korean Cell Line Bank (Seoul, Republic of Korea). CWR22Rv1 cells were purchased from ATCC (Manassas, VA, USA).