Optimization of Ultrasound-Assisted Extraction, HPLC and UHPLC-ESI-Q-TOF-MS/MS Analysis of Main Macamides and Macaenes from Maca (Cultivars of Lepidium meyenii Walp).

Ultrasound-assisted extraction (UAE), using petroleum ether as the solvent, was systematically applied to extract main macamides and macaenes from Maca hypocotyls. Extraction yield was related with four variables, including ratio of solution to solid, extraction temperature, extraction time, and extraction power. On the basis of response surface methodology (RSM), the optimal conditions were determined to be the ratio of solution to solid as 10:1 (mL/g), the extraction temperature of 40 °C, the extraction time of 30 min, and the extraction power of 200 W. Based on the optimal extraction method of UAE, the total contents of ten main macamides and two main macaenes of Maca cultivated in twenty different areas of Tibet were analyzed by HPLC and UHPLC-ESI-Q-TOF-MS/MS. This study indicated that UAE was able to effectively extract macamides alkaloids from Maca hypocotyls. Quantitative analysis showed that geographical origins, not ecotypes, played a more important role on the accumulation of active macamides in Maca.

A Strategy for Simultaneous Isolation of Less Polar Ginsenosides, Including a Pair of New 20-Methoxyl Isomers, from Flower Buds of Panax ginseng.

The present study was designed to simultaneously isolate the less polar ginsenosides from the flower buds of Panax ginseng (FBPG). Five ginsenosides, including a pair of new 20-methoxyl isomers, were extracted from FBPG and purified through a five-step integrated strategy, by combining ultrasonic extraction, Diaion Hp-20 macroporous resin column enrichment, solid phase extraction (SPE), reversed-phase high-performance liquid chromatography (RP-HPLC) analysis and preparation, and nuclear magnetic resonance (NMR) analysis. The quantification of the five ginsenosides was also discussed by a developed method with validations within acceptable limits. Ginsenoside Rg5 showed content of about 1% in FBPG. The results indicated that FBPG might have many different ginsenosides with diverse chemical structures, and the less polar ginsenosides were also important to the quality control and standardization of FBPG.

Novel SLC22A16 polymorphisms and influence on doxorubicin pharmacokinetics in Asian breast cancer patients.

OBJECTIVE: To identify novel polymorphisms in the solute carrier SLC22A16 gene and determine their influence on the pharmacokinetics of doxorubicin and doxorubicinol in Asian breast cancer patients. METHODS: SLC22A16 coding regions were screened in a total of 400 healthy subjects belonging to three distinct Asian ethnic groups (Chinese [n = 100], Malays [n = 100] and Indians [n = 100]) and in the Caucasian population (n = 100). Pharmacokinetic parameters of doxorubicin and doxorubicinol were estimated in Asian breast cancer patients undergoing adjuvant chemotherapy to investigate genotype-phenotype correlations. RESULTS: Four novel polymorphisms (c.146A>G [exon 2], c.312T>C, c.755T>C [exon 4] and c.1226T>C [exon 5]) were identified. The genotypic frequency of the homozygous c.146GG polymorphism was approximately twofold higher in the healthy Chinese (13%) & Malay (18%) populations compared with the Indian (7%) and Caucasian (9%) populations. The genotypic frequency of the c.1226T>C polymorphism was observed to be significantly higher among the Caucasian (11%) and Indian (8%) study subjects compared with the Chinese (1%) and Malay (1%) ethnic groups (p < 0.005 in each case). Breast cancer patients harboring the 146GG genotype showed a trend towards higher exposure levels to doxorubicin (AUC(0 negative infinity)/dose/body surface area [BSA] [hm(-5)]: 21.6; range: 18.8-27.7) compared with patients with either the reference genotype (AUC(0 negative infinity)/dose/BSA[hm(-5)]: 17.4; range: 8.2-26.3, p = 0.066) or heterozygotes (AUC(0 negative infinity)/dose/BSA[hm(-5)]: 15.4; range: 6.2-38.0, p = 0.055). The exposure levels of doxorubicinol were also higher in patients harboring the variant 146GG genotype (AUC(0 negative infinity)/dose/BSA[hm(-5)]: 13.3; range: 8.8-21.7) when compared with patients harboring the reference genotype (AUC(0 negative infinity)/dose/BSA[hm(-5)]): 9.8; range: 6.1-24.3, p = 0.137) or heterozygotes (AUC(0 negative infinity)/dose/BSA[hm(-5)]: 8.98; range: 3.7-20.6, p = 0.047). CONCLUSION: Among the four novel SLC22A16 polymorphisms identified, the c.146A>G and c.1226T>C polymorphisms exhibited interethnic variations in allele and genotype frequencies. This exploratory study suggests that the c.146A>G variation could contribute to the variations in the pharmacokinetics of doxorubicin and doxorubicinol in Asian cancer patients. Further in vitro studies are required to determine the functional impact of these novel polymorphisms on doxorubicin pharmacokinetics in cancer patients.