In July 2018, certain valsartan-containing drugs were voluntary recalled in Japan owing to contamination with N-nitrosodimethylamine (NDMA), a probable human carcinogen. In this study, an HPLC method was developed for the quantitative detection of NDMA simultaneously eluted with valsartan. Good linearity with a correlation coefficient (R²) > 0.999 was achieved over the concentration range of 0.011–7.4 µg/mL. The limits of detection and quantification were 0.0085 μg/mL and 0.0285 μg/mL, respectively. When the recalled valsartan samples were subjected to this method, the observed NDMA contents were in agreement with the reported values, indicating that our method achieved sufficient linearity, accuracy, and precision to detect NDMA in valsartan drug substances and products. Moreover, six samples (valsartan drug substances and tablet formulations), which had a possibility for NDMA contamination, were analyzed; none of the samples contained NDMA at detectable levels. Our method would be useful for the rapid screening and quantification of NDMA impurity in valsartan drug substances and products.

Many psychotropic substances are easily available in Japan via the Internet, thus the spread of drug abuse is becoming more serious problem. To avoid drug abuse, 32 substances have been controlled in Japan since April in 2007 by the Pharmaceutical Affairs Law as designated substances (Shitei-Yakubutsu, classified as 11 tryptamines, 11 phenethylamines, 2 piperazines, 6 alkyl nitrites, 1 diterpene and 1 plant). Although the distributions of these drugs have been decreased through this regulation, new designer drugs are still being found. In this study, we detected 7 designer drugs in 15 products, which purchased just before the amendment of the law, by NMR, GC-MS and LC-MS analyses. Three methylone derivertives (1-(3,4-methylenedioxyphenyl-2-(pyrrolidin-1-yl)-1-pentanone: MDPV, 2-methylamino-1-(3,4-methylenedioxyphenyl)butan-1-one: bk-MBDB, 2-ethylamino-1-(3,4-methylenedioxyphenyl)propan-1-one): bk-MDEA, a MDMA derivative (N-hydroxy-1-(3,4-methylenedioxyphenyl)-2-aminopropane: N-OH MDMA), a methamphetamine derivative (N-methyl-1-(4-fluorophenyl)propan-2-amine: N-Me-4-FMP), a tryptamine derivative (5-methoxy-N-ethyl-N-isopropyltryptamine: 5-MeO-EIPT) and indan-2-amine were detected. 5-MeO-EIPT was newly identified in this study.

Six new psychoactive substances were identified together with two other substances (compounds 1–8) in illegal products by our ongoing survey in Japan between January and July 2014. A new synthetic cannabinoid, FDU-NNEI [1-(4-fluorobenzyl)-N-(naphthalen-1-yl)-1H-indole-3-carboxamide, 2], was detected with the newly distributed synthetic cannabinoid FDU-PB-22 (1). Two 2H-indazole isomers of synthetic cannabinoids, AB-CHMINACA 2H-indazole analog (3) and NNEI 2H-indazole analog (4), were newly identified with 1H-indazoles [AB-CHMINACA and NNEI indazole analog (MN-18)]. In addition, 2-methylpropyl N-(naphthalen-1-yl) carbamate (5) and isobutyl 1-pentyl-1H-indazole-3-carboxylate (6) were detected in illegal products. Compound 6 is considered to be a by-product of the preparation of NNEI indazole analog from compound 5 and 1-pentyl-1H-indazole. A phenethylamine derivative, N–OH-EDMA [N-hydroxy-3,4-ethylenedioxy-N-methylamphetamine, 7], and a cathinone derivative, dimethoxy-α-PHP (dimethoxy-α-pyrrolidinohexanophenone, 8), were newly identified in illegal products. Among them, compounds 1 and 8 have been controlled as designated substances (Shitei-Yakubutsu) under the Pharmaceutical Affairs Law in Japan since August and November 2014, respectively.