ABSTRACT
Concerns about health hazards associated with the consumption of trans-delta-8-tetrahydrocannabinol products were highlighted in public health advisories from the U.âS. Food and Drug Administration and U.âS. Centers for Disease Control and Prevention. Simple and rapid quantitative methods to determine trans-delta-8-tetrahydrocannabinol impurities are vital to analyze such products. In this study, a gas chromatography-flame ionization detection method was developed and validated for the determination of delta-8-tetrahydrocannabinol and some of its impurities (recently published) found in synthesized trans-delta-8-tetrahydrocannabinol raw material and included olivetol, cannabicitran, Δ 8-cis-iso-tetrahydrocannabinol, Δ 4-iso-tetrahydrocannabinol, iso-tetrahydrocannabifuran, cannabidiol, Δ 4,8-iso-tetrahydrocannabinol, Δ 8-iso-tetrahydrocannabinol, 4,8-epoxy-iso-tetrahydrocannabinol, trans-Δ 9-tetrahydrocannabinol, 8-hydroxy-iso-THC, 9α-hydroxyhexahydrocannabinol, and 9ß-hydroxyhexahydrocannabinol. Validation of the method was assessed according to the International Council for Harmonization guidelines and confirmed linearity with R2 ≥ 0.99 for all the target analytes. The limit of detection and limit of quantitation were 1.5 and 5 µg/mL, respectively, except for olivetol, which had a limit of detection of 3 µg/mL and a limit of quantitation of 10 µg/mL. Method precision was calculated as % relative standard deviation and the values were less than 8.4 and 9.9% for the intraday precision and inter-day precision, respectively. The accuracy ranged from 85 to 118%. The method was then applied to the analysis of 21 commercially marketed vaping products claiming to contain delta-8-tetrahydrocannabinol. The products analyzed by this method have various levels of these impurities, with all products far exceeding the 0.3% of trans-Δ 9-tetrahydrocannabinol limit for hemp under the Agriculture Improvement Act of 2018. The developed gas chromatography-flame ionization detection method can be an important tool for monitoring delta-8-tetrahydrocannabinol impurities in commercial products.
Subject(s)
Dronabinol , Dronabinol/analogs & derivatives , Resorcinols , Vaping , Dronabinol/analysis , Gas Chromatography-Mass Spectrometry/methods , Chromatography, GasABSTRACT
For decades, Cannabis sativa had been illegal to sell or consume around the world, including in the United States. However, in light of the recent 2018 Farm Bill and the legalization of hemp across the US, various cannabis preparations have flooded the market, making it essential to be able to quantitate the levels of the different acidic and neutral cannabinoids in C. sativa and to have a complete cannabinoid profile of the different chemovars of the cannabis plant. A GC-FID method was developed and validated for the analysis of 20 acidic and neutral cannabinoids as trimethylsilyl (TMS) derivatives. The analyzed cannabinoids include cannabidivarinic acid (CBDVA), cannabidiolic acid (CBDA), cannabinolic acid (CBNA), cannabielsoic acid (CBEA), cannabicyclolic acid (CBLA), cannabichromenic acid (CBCA), trans-Δ9-tetrahydrocannabivarinic acid (Δ9-THCVA), trans-Δ9-tetrahydrocannabinolic acid A (Δ9-THCAA), cannabigerolic acid (CBGA), cannabidiol (CBD), cannabicyclol (CBL), cannabidivarin (CBDV), trans-Δ9-tetrahydrocannabivarin (THCV), cannabichromene (CBC), trans-Δ8-tetrahydrocannabinol (Δ8-THC), trans-Δ9-tetrahydrocannabinol (Δ9-THC), cannabigerol (CBG), cannabinol (CBN), cannabicitran (CBT), and cannabielsoin (CBE). The method limit of detection (LOD) was as low as 0.1 µg/mL, while the limit of quantitation ranged from 0.25 µg/mL to 0.5 µg/mL. The precision (%RSD) was < 10%, while trueness ranged from 90â-â107%. The developed method is simple, accurate, and sensitive for the quantitation of all 20 acidic and neutral cannabinoids. Finally, the proposed method was successfully applied to the quantitation of the cannabinoids in different cannabis chemovars grown at the University of Mississippi.
Subject(s)
Cannabinoids , Cannabis , Cannabinoids/analysis , Limit of DetectionABSTRACT
A liquid chromatography-tandem mass spectrometry single-laboratory validation was performed for the detection and quantification of the 10 major cannabinoids of cannabis, namely, (-)-trans-Δ9-tetrahydrocannabinol, cannabidiol, cannabigerol, cannabichromene, tetrahydrocannabivarian, cannabinol, (-)-trans-Δ8-tetrahydrocannabinol, cannabidiolic acid, cannabigerolic acid, and Δ9-tetrahydrocannabinolic acid-A, in the root extract of Cannabis sativa. Acetonitrileâ:âmethanol (80â:â20, v/v) was used for extraction; d3-cannabidiol and d3- tetrahydrocannabinol were used as the internal standards. All 10 cannabinoids showed a good regression relationship with r2 > 0.99. The validated method is simple, sensitive, and reproducible and is therefore suitable for the detection and quantification of these cannabinoids in extracts of cannabis roots. To our knowledge, this is the first report for the quantification of cannabinoids in cannabis roots.
Subject(s)
Cannabinoids/analysis , Cannabis/chemistry , Chromatography, Liquid/methods , Plant Extracts/chemistry , Plant Roots/chemistry , Tandem Mass Spectrometry/methodsABSTRACT
Cannabis (Cannabis sativa L.) is an annual herbaceous plant that belongs to the family Cannabaceae. Trans-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) are the two major phytocannabinoids accounting for over 40% of the cannabis plant extracts, depending on the variety. At the University of Mississippi, different strains of C. sativa, with different concentration ratios of CBD and Δ9-THC, have been tissue cultured via micropropagation and cultivated. A GC-FID method has been developed and validated for the qualitative and quantitative analysis of acid and neutral cannabinoids in C. sativa extracts. The method involves trimethyl silyl derivatization of the extracts. These cannabinoids include tetrahydrocannabivarian, CBD, cannabichromene, trans-Δ8-tetrahydrocannabinol, Δ9-THC, cannabigerol, cannabinol, cannabidiolic acid, cannabigerolic acid, and Δ9-tetrahydrocannabinolic acid-A. The concentration-response relationship of the method indicated a linear relationship between the concentration and peak area ratio with R2 > 0.999 for all 10 cannabinoids. The precision and accuracy of the method were found to be ≤ 15% and ± 5%, respectively. The limit of detection range was 0.11â-â0.19 µg/mL, and the limit of quantitation was 0.34â-â0.56 µg/mL for all 10 cannabinoids. The developed method is simple, sensitive, reproducible, and suitable for the detection and quantitation of acidic and neutral cannabinoids in different extracts of cannabis varieties. The method was applied to the analysis of these cannabinoids in different parts of the micropropagated cannabis plants (buds, leaves, roots, and stems).
Subject(s)
Cannabinoids/analysis , Cannabis/chemistry , Flame Ionization/methods , Plant Extracts/chemistry , Cannabidiol/analysis , Dronabinol/analysisABSTRACT
This study sought to determine whether the cannabis constituent cannabidiol attenuates the development of morphine reward in the conditioned place preference paradigm. Separate groups of mice received either saline or morphine in combination with one of four doses of cannabidiol using three sets of drug/no-drug conditioning trials. After drug-place conditioning, morphine mice displayed robust place preference that was attenuated by 10 mg/kg cannabidiol. Further, when administered alone, this dose of cannabidiol was void of rewarding and aversive properties. The finding that cannabidiol blocks opioid reward suggests that this compound may be useful in addiction treatment settings.
Subject(s)
Cannabidiol/pharmacology , Morphine/pharmacology , Spatial Behavior/drug effects , Animals , Conditioning, Operant/drug effects , Dose-Response Relationship, Drug , Male , Mice , Mice, Inbred C57BL , Morphine/antagonists & inhibitors , RewardABSTRACT
Purpose: The aim of the present study was to evaluate the utility of the relatively hydrophilic Δ9-tetrahydrocannabinol (THC) prodrugs, mono and di-valine esters (THC-Val and THC-Val-Val) and the amino acid (valine)-dicarboxylic acid (hemisuccinate) ester (THC-Val-HS), with respect to ocular penetration and intraocular pressure (IOP) lowering activity. THC, timolol, and pilocarpine eye drops were used as controls. Methods: THC-Val, THC-Val-Val, and THC-Val-HS were synthesized and chemically characterized. Aqueous solubility and in vitro transcorneal permeability of THC and the prodrugs, in the presence of various surfactants and cyclodextrins, were determined. Two formulations were evaluated for therapeutic activity in the α-chymotrypsin induced rabbit glaucoma model, and the results were compared against controls comprising of THC emulsion and marketed timolol maleate and pilocarpine eye drops. Results: THC-Val-HS demonstrated markedly improved solubility (96-fold) and in vitro permeability compared to THC. Selected formulations containing THC-Val-HS effectively delivered THC to the anterior segment ocular tissues in the anesthetized rabbits: 62.1 ng/100 µL of aqueous humor (AH) and 51.4 ng/50 mg of iris ciliary bodies (IC) (total THC). The duration and extent of IOP lowering induced by THC-Val-HS was 1 hour longer and 10% greater, respectively, than that obtained with THC and was comparable with the pilocarpine eye drops. Timolol ophthalmic drops, however, exhibited a longer duration of activity. Both THC and THC-Val-HS were detected in the ocular tissues following multiple dosing of THC-Val-HS in conscious animals. The concentration of THC in the iris-ciliary bodies at the 60- and 120-minute time points (53 and 57.4 ng/50 mg) were significantly greater than that of THC-Val-HS (24.2 and 11.3 ng/50 mg). Moreover, at the two time points studied, the concentration of THC was observed to increase or stay relatively constant, whereas THC-Val-HS concentration decreased by at least 50%. A similar trend was observed in the retina-choroid tissues. Conclusions: A combination of prodrug derivatization and formulation development approaches significantly improved the penetration of THC into the anterior segment of the eye following topical application. Enhanced ocular penetration resulted in significantly improved IOP-lowering activity.
Subject(s)
Aqueous Humor/metabolism , Cornea/metabolism , Dronabinol/pharmacokinetics , Glaucoma/drug therapy , Intraocular Pressure/drug effects , Prodrugs/pharmacokinetics , Vitreous Body/metabolism , Animals , Aqueous Humor/drug effects , Biological Availability , Cannabinoid Receptor Agonists/pharmacokinetics , Cornea/drug effects , Disease Models, Animal , Drug Evaluation, Preclinical , Glaucoma/metabolism , Glaucoma/physiopathology , Male , Ophthalmic Solutions , Rabbits , Vitreous Body/drug effectsABSTRACT
Sativex, a cannabinoid extract with a 1â:â1 ratio of tetrahydocannabinol and cannabidiol, has been shown to alleviate neuropathic pain associated with chemotherapy. This research examined whether tetrahydocannabinol or cannabidiol alone could attenuate or prevent cisplatin-induced tactile allodynia. In experiment 1, mice (C57BL/6) received eight administrations of 2.3 mg/kg cisplatin or saline solution IP every other day to induce tactile allodynia. Mice were then administered vehicle, 100 mg/kg gabapentin, 2 mg/kg tetrahydocannabinol, or 2 mg/kg cannabidiol IP and tested 60 min later on an electronic Von Frey. In experiment 2, prevention studies, cannabidiol (0.0, 0.5, 1.0, and 2.0 mg/kg) or tetrahydocannabinol (0.0, 0.5, 1.0, and 2.0 mg/kg) was given IP 30 min prior to cisplatin administration (2.3 or 1.0 mg/kg) utilizing a six-dose alternate day protocol. In both studies, tactile responses to the hind paws were quantified in g of force using an electronic Von Frey prior to and after the cisplatin administration protocol. Cisplatin produced a reduction in g of force indicative of neuropathy that was attenuated by gabapentin, tetrahydocannabinol, and cannabidiol but not prevented by either cannabinoid. These data demonstrate that each of the major constituents of Sativex alone can achieve analgesic effects against cisplatin neuropathy.
Subject(s)
Analgesics/therapeutic use , Cannabidiol/therapeutic use , Dronabinol/therapeutic use , Hyperalgesia/drug therapy , Animals , Cisplatin , Drug Combinations , Hyperalgesia/chemically induced , Male , Mice , Mice, Inbred C57BL , Plant Extracts/therapeutic useABSTRACT
An HPLC single-laboratory validation was performed for the detection and quantification of the 11 major cannabinoids in most cannabis varieties, namely, cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), cannabigerol (CBG), cannabidiol (CBD), tetrahydrocannabivarin (THCV), cannabinol (CBN), Δ9-trans-tetrahydrocannabinol (Δ9-THC), Δ8-trans-tetrahydrocannabinol (Δ8-THC), cannabicyclol (CBL), cannabichromene (CBC), and Δ9-tetrahydrocannabinolic acid-A (THCAA). The analysis was carried out on the biomass and extracts of these varieties. Methanol-chloroform (9:1, v/v) was used for extraction, 4-androstene-3,17-dione was used as the internal standard, and separation was achieved in 22.2 min on a C18 column using a two- step gradient elution. The method was validated for the 11 cannabinoids. The concentration-response relationship of the method indicated a linear relationship between the concentration and peak area with r2 values of >0.99 for all 11 cannabinoids. Method accuracy was determined through a spike study, and recovery ranged from 89.7 to 105.5% with an RSD of 0.19 to 6.32% for CBDA, CBD, THCV, CBN, Δ9-THC, CBL, CBC, and THCAA; recovery was 84.7, 84.2, and 67.7% for the minor constituents, CBGA, CBG, and Δ8-THC, respectively, with an RSD of 2.58 to 4.96%. The validated method is simple, sensitive, and reproducible and is therefore suitable for the detection and quantification of these cannabinoids in different types of cannabis plant materials.
Subject(s)
Biomass , Cannabinoids/analysis , Cannabis/chemistry , Chromatography, High Pressure Liquid/methods , Plant Extracts/analysisABSTRACT
In a previous publication, we reported on the analysis of several dietary supplement/exercise formulas and the quantitation of N,α-diethylphenethylamine (N,α-ETH, 3: ). In this article we report on the reanalysis of these products using LC-MS-MS and GC-MS methods capable of clearly separating the N,α-isomer ( 3: ) from its N,ß-isomer (N,ß-ETH, 4: ). The reanalysis, by both methods, showed that all samples previously reported as containing N,α-ETH ( 3: ) do contain only that isomer with no detectable concentrations of the N,ß-ETH ( 4: ).
Subject(s)
Chromatography, Liquid , Dietary Supplements/analysis , Methamphetamine/analogs & derivatives , Tandem Mass Spectrometry , Calibration , Chromatography, Liquid/standards , Gas Chromatography-Mass Spectrometry , Isomerism , Methamphetamine/analysis , Methamphetamine/chemistry , Molecular Structure , Reference Standards , Reproducibility of Results , Tandem Mass Spectrometry/standardsABSTRACT
There has been a recent rise in the number of cases of athletes being banned from competition because of positive tests for prohibited substances in their biological specimens. Most of these substances are on the World Anti-Doping Agency (WADA) prohibited list, while others are not specifically named on the list. N-Ethyl-α-ethyl-phenethylamine (ETH), a derivative of phenethylamine (PEA), is one of these unlisted substances and shares chemical and biological effects to the amphetamines, which are listed on the WADA prohibited substances list. It is classified as Category 6B stimulant on the list. This study was directed toward the development of an liquid chromatography tandem mass spectrometry (LC-MS-MS) method for the analysis of ETH in performance-enhancing dietary supplement. A standard was prepared and confirmed by spectroscopic analysis, which was then used to develop the analytical procedure. The procedure was validated and found to have an limit of detection of 2.5 ng/mL, limit of quantification of 5 ng/mL and upper limit of linearity of 500 ng/mL, with within-day variability at the 10-ng/mL level range of 3.88-7.89% (n = 6) and 1.39-3.36% (n = 6) for the 100-ng/mL level. The day-to-day variability was 9.8% for the low control and 3.1% for the high control. The method was used to analyze a variety of dietary supplements for ETH as well as PEA and its N, N-diethyl derivative (NDP).
Subject(s)
Butylamines/analysis , Chromatography, Liquid , Dietary Supplements/analysis , Doping in Sports , Performance-Enhancing Substances/analysis , Phenethylamines/analysis , Substance Abuse Detection/methods , Tandem Mass Spectrometry , Calibration , Chromatography, Liquid/standards , Humans , Limit of Detection , Magnetic Resonance Spectroscopy , Predictive Value of Tests , Reference Standards , Reproducibility of Results , Substance Abuse Detection/standards , Tandem Mass Spectrometry/standardsABSTRACT
Methylhexaneamine (MHA) has been marketed in dietary supplements based on arguments that it is a constituent of geranium (Pelargonium graveolens) leaves, stems, roots or oil, and therefore qualifies as a dietary ingredient. The purpose of this study is to determine whether P. graveolens plant material (authenticated) or its oil contains detectable quantities of MHA. Two analytical methods were developed for the analysis of MHA in P. graveolens using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry. The results were further confirmed using liquid chromatography-high-resolution mass spectrometry. Twenty commercial volatile oils, three authenticated volatile oils and authenticated P. graveolens leaves and stems (young and mature, and fresh and dried) were analyzed for MHA content. In addition, three dietary supplements containing MHA that alleged P. graveolens as the source are analyzed for their MHA content. The data show that none of the authenticated P. graveolens essential oils or plant material, nor any commercial volatile oil of Pelargonium (geranium oil) contain MHA at detectable levels (limit of detection: 10 ppb). The dietary supplements that contained MHA as one of their ingredients (allegedly from geranium or geranium stems) contained large amounts of MHA. The amounts of MHA measured are incompatible with the use of reasonable amounts of P. graveolens extract or concentrate, suggesting that MHA was of synthetic origin.
Subject(s)
Amines/analysis , Dietary Supplements , Pelargonium/chemistry , Plant Oils/analysis , Amines/chemistry , Gas Chromatography-Mass Spectrometry/methods , Geranium/chemistry , Limit of Detection , Oils, Volatile/analysis , Oils, Volatile/chemistry , Plant Leaves/chemistry , Plant Oils/chemistry , Reproducibility of Results , Tandem Mass Spectrometry/methodsABSTRACT
The double-edged sword of antibiotic use in the fight against disease has saved countless lives at the cost of an escalation in pathogenic bacteria with increased resistance to multiple antibiotic classes. Reduction of resistance is a complicated multi-step endeavor that requires a sustained international effort of reduced utilization, infection control and development of effective and economical antimicrobial agents. The carbapenems are beta-lactam antibiotics that are stable to most beta-lactamases. They have potent bactericidal activity against a wide range of Gram-positive and Gram-negative aerobic bacteria as well as against anaerobic bacteria, while being safe, efficacious and tolerable. The use of carbapenems in hospitals has therefore been restricted to the empirical treatment of critical patients with a variety of serious infections, e.g., nosocomial pneumonia, septicemia, meningitis and cystic fibrosis. This article reviews patents claiming carbapenem antibacterial agents published from 2004-2008.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Carbapenems/chemical synthesis , Carbapenems/therapeutic use , Animals , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/pharmacokinetics , Bacterial Infections/microbiology , Carbapenems/adverse effects , Carbapenems/pharmacokinetics , Drug Discovery , Drug Resistance, Multiple, Bacterial , Humans , Microbial Sensitivity Tests , Molecular Structure , Patents as Topic , Structure-Activity Relationship , Treatment OutcomeABSTRACT
Naturally occurring cannabinoids (phytocannabinoids) are biosynthetically related terpenophenolic compounds uniquely produced by the highly variable plant, Cannabis sativa L. Natural and synthetic cannabinoids have been extensively studied since the discovery that the psychotropic effects of cannabis are mainly due to Delta(9)-THC. However, cannabinoids exert pharmacological actions on other biological systems such as the cardiovascular, immune and endocrine systems. Most of these effects have been attributed to the ability of these compounds to interact with the cannabinoid CB1 and CB2 receptors. The FDA approval of Marinol, a product containing synthetic Delta(9)-THC (dronabinol), in 1985 for the control of nausea and vomiting in cancer patients receiving chemotherapy, and in 1992 as an appetite stimulant for AIDS patients, has further intensified the research interest in these compounds. This article reviews patents (2003-2007) that describe methods for isolation of cannabinoids from cannabis, chemical and chromatographic methods for their purification, synthesis, and potential therapeutic applications of these compounds.
Subject(s)
Cannabinoids/chemical synthesis , Cannabinoids/therapeutic use , Drug Discovery/methods , Psychotropic Drugs/therapeutic use , Animals , Appetite Stimulants/pharmacology , Appetite Stimulants/therapeutic use , Cannabinoids/chemistry , Cannabinoids/pharmacology , Cardiovascular Diseases/drug therapy , Cardiovascular System/drug effects , Humans , Psychotropic Drugs/chemical synthesis , Psychotropic Drugs/pharmacology , Receptors, Cannabinoid/classification , Receptors, Cannabinoid/physiology , Structure-Activity RelationshipABSTRACT
Analogs of the malaria therapeutic, artemisinin, possess in vitro and in vivo anticancer activity. In this study, two dimeric artemisinins (NSC724910 and 735847) were studied to determine their mechanism of action. Dimers were >1,000 fold more active than monomer and treatment was associated with increased reactive oxygen species (ROS) and apoptosis induction. Dimer activity was inhibited by the antioxidant L-NAC, the iron chelator desferroxamine and exogenous hemin. Similarly, induction of heme oxygenase (HMOX) with CoPPIX inhibited activity, whereas inhibition of HMOX with SnPPIX enhanced it. These results emphasize the importance of iron, heme and ROS in activity. Microarray analysis of dimer treated cells identified DNA damage, iron/heme and cysteine/methionine metabolism, antioxidant response, and endoplasmic reticulum (ER) stress as affected pathways. Detection of an ER-stress response was relevant because in malaria, artemisinin inhibits pfATP6, the plasmodium orthologue of mammalian sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPases (SERCA). A comparative study of NSC735847 with thapsigargin, a specific SERCA inhibitor and ER-stress inducer showed similar behavior in terms of transcriptomic changes, induction of endogenous SERCA and ER calcium mobilization. However, thapsigargin had little effect on ROS production, modulated different ER-stress proteins and had greater potency against purified SERCA1. Furthermore, an inactive derivative of NSC735847 that lacked the endoperoxide had identical inhibitory activity against purified SERCA1, suggesting that direct inhibition of SERCA has little inference on overall cytotoxicity. In summary, these data implicate indirect ER-stress induction as a central mechanism of artemisinin dimer activity.
Subject(s)
Antineoplastic Agents/pharmacology , Artemisinins/pharmacology , Endoplasmic Reticulum/drug effects , Heme Oxygenase-1/metabolism , Heme/metabolism , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Acetylcysteine/analogs & derivatives , Acetylcysteine/pharmacology , Antioxidants/pharmacology , Apoptosis/drug effects , Artemisia/chemistry , Biomarkers/metabolism , Blotting, Western , Calcium/metabolism , Cell Cycle/drug effects , Dimerization , Endoplasmic Reticulum/metabolism , Enzyme Inhibitors/pharmacology , Gene Expression Profiling , Humans , Lysine/analogs & derivatives , Lysine/pharmacology , Oligonucleotide Array Sequence Analysis , Sarcoplasmic Reticulum Calcium-Transporting ATPases/antagonists & inhibitors , Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism , Thapsigargin/pharmacologyABSTRACT
Malaria is the number one disease in the world responsible for 1-3 million deaths each year. The world wide number of malaria patients is estimated at 400 to 900 million. Approximately one third of the world's population lives in malaria-endemic areas, including Central and South America, Asia, and Africa. Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale and Plasmodium malariae are malaria parasites responsible for infecting humans. Mosquitoes that carry malaria parasites have become resistant to insecticides, and the deadliest parasites have become resistant to previously effective antimalarial drugs such as chloroquine, quinine and other clinically used agents. Because of the widespread incidence of malaria in certain parts of the world and because of the increasing parasite resistance to standard anti-malarial agents, there is an urgent need for introducing new effective drugs. This review presents the recent patents that reveal development of novel antimalarial drugs.